{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:13:15Z","timestamp":1791663195810,"version":"4.3.4"},"reference-count":127,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Periodontology 2000"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Periodontitis is a complex inflammatory disease in which the host genome, in conjunction with extrinsic factors, determines susceptibility and progression. Genetic predisposition is the strongest risk factor in the first decades of life. As people age, chronic exposure to the periodontal microbiome puts a strain on the proper maintenance of barrier function. This review summarizes our current knowledge on genetic risk factors implicated in periodontitis, derived (i) from hypothesis\u2010free systematic whole genome\u2010profiling studies (genome\u2010wide association studies [GWAS] and quantitative trait loci [QTL] mapping studies), and independently validated through further unbiased approaches; (ii) from monogenic and oligogenic forms of periodontitis; and (iii) from syndromic forms of periodontitis. The genes include, but are not limited to, <jats:italic>SIGLEC5<\/jats:italic>, <jats:italic>PLG, ROBO2<\/jats:italic>, <jats:italic>ABCA1, PF4,<\/jats:italic> and <jats:italic>CTSC<\/jats:italic>. Notably, <jats:italic>CTSC<\/jats:italic> and <jats:italic>PLG<\/jats:italic> gene mutations were also identified in non\u2010syndromic and syndromic forms of prepubertal and early\u2010onset periodontitis. The functions of the identified genes in this review suggest that the pathways affected by the periodontitis\u2010associated gene variants converge in functions involved in the maintenance and repair of structural integrity of the periodontal tissues. Particularly, these genes play a role in the healing of inflamed and ulcerated periodontal tissues, including roles in fibrinolysis, extrusion of cellular debris, extracellular matrix remodeling and angiogenesis. Syndromes that include periodontitis in their phenotype indicate that neutrophils play an important role in the regulation of inflammation in the periodontium. The established genetic susceptibility genes therefore collectively provide new insights into the molecular mechanisms and plausible causal factors underlying periodontitis.<\/jats:p>","DOI":"10.1111\/prd.12622","type":"journal-article","created":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T05:45:42Z","timestamp":1739598342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Genetic risk variants implicate impaired maintenance and repair of periodontal tissues as causal for periodontitis\u2014A synthesis of recent findings"],"prefix":"10.1111","author":[{"given":"Arne S.","family":"Schaefer","sequence":"first","affiliation":[{"name":"Department of Periodontology, Oral Medicine and Oral Surgery, Institute for Dental and Craniofacial Sciences Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t Zu Berlin and Berlin Institute of Health Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7750-5010","authenticated-orcid":false,"given":"Luigi","family":"Nibali","sequence":"additional","affiliation":[{"name":"Periodontology Unit, Faculty of Dentistry, Oral and Craniofacial Sciences Centre for Host Microbiome Interactions, King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha","family":"Zoheir","sequence":"additional","affiliation":[{"name":"Periodontology Unit, Faculty of Dentistry, Oral and Craniofacial Sciences Centre for Host Microbiome Interactions, King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki M.","family":"Moutsopoulos","sequence":"additional","affiliation":[{"name":"Oral Immunity and Infection Section National Institute of Dental and Craniofacial Research, National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8794-552X","authenticated-orcid":false,"given":"Bruno G.","family":"Loos","sequence":"additional","affiliation":[{"name":"Department of Periodontology Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"issue":"1","key":"e_1_2_8_2_1","first-page":"S74","article-title":"Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: consensus report of workgroup 1 of the 2017 world workshop on the classification of periodontal and Peri\u2010implant diseases and conditions","volume":"89","author":"Chapple ILC","year":"2018","journal-title":"J Periodontol"},{"issue":"10","key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1111\/jcpe.13520","article-title":"Retrospective long\u2010term analysis of tooth loss over 20\u2009years in a specialist practice setting: Periodontally healthy\/gingivitis and compromised patients","volume":"48","author":"Junge T","year":"2021","journal-title":"J Clin Periodontol"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/jcpe.13253","article-title":"Endpoints of active periodontal therapy","volume":"47","author":"Loos BG","year":"2020","journal-title":"J Clin Periodontol"},{"issue":"1","key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/prd.12297","article-title":"The role of inflammation and genetics in periodontal disease","volume":"83","author":"Loos BG","year":"2020","journal-title":"Periodontol 2000"},{"issue":"8","key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1016\/S0531-5565(99)00068-6","article-title":"Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load","volume":"34","author":"Franceschi C","year":"1999","journal-title":"Exp Gerontol"},{"issue":"9","key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci L","year":"2018","journal-title":"Nat Rev Cardiol"},{"issue":"5","key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s00281-020-00806-z","article-title":"The interplay between immunosenescence and age\u2010related diseases","volume":"42","author":"Barbe\u2010Tuana F","year":"2020","journal-title":"Semin Immunopathol"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/prd.12135","article-title":"Aging, inflammation, immunity and periodontal disease","volume":"72","author":"Ebersole JL","year":"2016","journal-title":"Periodontol 2000"},{"issue":"18","key":"e_1_2_8_10_1","first-page":"S12","article-title":"Dental biofilm: ecological interactions in health and disease","volume":"44","author":"Marsh PD","year":"2017","journal-title":"J Clin Periodontol"},{"issue":"9","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23095142","article-title":"Impact of oral microbiome in periodontal health and periodontitis: a critical review on prevention and treatment","volume":"23","author":"Di Stefano M","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"2","key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1016\/j.cub.2013.11.036","article-title":"Trade\u2010offs","volume":"24","author":"Garland T","year":"2014","journal-title":"Curr Biol"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1600-0757.2012.00450.x","article-title":"Periodontitis: a host\u2010mediated disruption of microbial homeostasis. Unlearning learned concepts","volume":"62","author":"Bartold PM","year":"2013","journal-title":"Periodontol 2000"},{"issue":"5","key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nri2294","article-title":"Resolving inflammation: dual anti\u2010inflammatory and pro\u2010resolution lipid mediators","volume":"8","author":"Serhan CN","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.3389\/fimmu.2017.01682","article-title":"Emerging concepts in the resolution of periodontal inflammation: a role for resolvin E1","volume":"8","author":"Balta MG","year":"2017","journal-title":"Front Immunol"},{"issue":"11","key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1177\/0022034514552491","article-title":"Global burden of severe periodontitis in 1990\u20102010: a systematic review and meta\u2010regression","volume":"93","author":"Kassebaum NJ","year":"2014","journal-title":"J Dent Res"},{"issue":"1","key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1177\/154405910608500113","article-title":"Full\u2010mouth tooth extraction lowers systemic inflammatory and thrombotic markers of cardiovascular risk","volume":"85","author":"Taylor BA","year":"2006","journal-title":"J Dent Res"},{"issue":"7","key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.cell.2018.05.051","article-title":"Common disease is more complex than implied by the Core gene Omnigenic model","volume":"173","author":"Wray NR","year":"2018","journal-title":"Cell"},{"issue":"6","key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1177\/0022034519842510","article-title":"What is the heritability of periodontitis? A Systematic Review","volume":"98","author":"Nibali L","year":"2019","journal-title":"J Dent Res"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1741-7015-10-5","article-title":"Towards a genuinely medical model for psychiatric nosology","volume":"10","author":"Nesse RM","year":"2012","journal-title":"BMC Med"},{"issue":"4","key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/ajpa.20831","article-title":"Maintenance versus growth: investigating the costs of immune activation among children in lowland Bolivia","volume":"136","author":"McDade TW","year":"2008","journal-title":"Am J Phys Anthropol"},{"issue":"2","key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1600-051X.2010.01653.x","article-title":"Periodontal genetics: a decade of genetic association studies mandates better study designs","volume":"38","author":"Schafer AS","year":"2011","journal-title":"J Clin Periodontol"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2010\/324719","article-title":"Gene polymorphisms in chronic periodontitis","volume":"2010","author":"Laine ML","year":"2010","journal-title":"Int J Dent"},{"issue":"6","key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1600-051X.2005.00806.x","article-title":"Identification of genetic risk factors for periodontitis and possible mechanisms of action","volume":"32","author":"Loos BG","year":"2005","journal-title":"J Clin Periodontol"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1469-1809.2005.00241.x","article-title":"Investigating the genetic determinants of cardiovascular disease using candidate genes and meta\u2010analysis of association studies","volume":"70","author":"Casas JP","year":"2006","journal-title":"Ann Hum Genet"},{"issue":"14","key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1001\/jama.297.14.1551","article-title":"Nonvalidation of reported genetic risk factors for acute coronary syndrome in a large\u2010scale replication study","volume":"297","author":"Morgan TM","year":"2007","journal-title":"JAMA"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/jcpe.12092","article-title":"Validation of reported genetic risk factors for periodontitis in a large\u2010scale replication study","volume":"40","author":"Schaefer AS","year":"2013","journal-title":"J Clin Periodontol"},{"issue":"7614","key":"e_1_2_8_28_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nature18642","article-title":"The genetic architecture of type 2 diabetes","volume":"536","author":"Fuchsberger C","year":"2016","journal-title":"Nature"},{"issue":"11","key":"e_1_2_8_29_1","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1038\/nn.4402","article-title":"Increased burden of ultra\u2010rare protein\u2010altering variants among 4,877 individuals with schizophrenia","volume":"19","author":"Genovese G","year":"2016","journal-title":"Nat Neurosci"},{"issue":"1","key":"e_1_2_8_30_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-10630-1","article-title":"Genome\u2010wide analysis of dental caries and periodontitis combining clinical and self\u2010reported data","volume":"10","author":"Shungin D","year":"2019","journal-title":"Nat Commun"},{"key":"e_1_2_8_31_1","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1093\/hmg\/ddx151","article-title":"A genome\u2010wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis","volume":"26","author":"Munz M","year":"2017","journal-title":"Hum Mol Genet"},{"key":"e_1_2_8_32_1","doi-asserted-by":"crossref","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue\u2010based map of the human proteome","volume":"347","author":"Uhlen M","year":"2015","journal-title":"Science"},{"issue":"5922","key":"e_1_2_8_33_1","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1126\/science.1168988","article-title":"CD24 and Siglec\u201010 selectively repress tissue damage\u2010induced immune responses","volume":"323","author":"Chen GY","year":"2009","journal-title":"Science"},{"key":"e_1_2_8_34_1","first-page":"551","article-title":"Periodontitis risk variants at SIGLEC5 impair ERG and MAFB binding","volume":"22","author":"Mueller R","year":"2021","journal-title":"J Dent Res"},{"issue":"11","key":"e_1_2_8_35_1","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1161\/ATVBAHA.122.318179","article-title":"Regulation of VWF (Von Willebrand factor) in inflammatory thrombosis","volume":"42","author":"Manz XD","year":"2022","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"9","key":"e_1_2_8_36_1","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1093\/emboj\/19.9.1987","article-title":"MafB is an inducer of monocytic differentiation","volume":"19","author":"Kelly LM","year":"2000","journal-title":"EMBO J"},{"issue":"1","key":"e_1_2_8_37_1","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/s41467-017-00738-7","article-title":"Transcriptional regulation of endothelial cell behavior during sprouting angiogenesis","volume":"8","author":"Jeong HW","year":"2017","journal-title":"Nat Commun"},{"issue":"1","key":"e_1_2_8_38_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41431-018-0265-5","article-title":"Meta\u2010analysis of genome\u2010wide association studies of aggressive and chronic periodontitis identifies two novel risk loci","volume":"27","author":"Munz M","year":"2019","journal-title":"Eur J Hum Genet"},{"issue":"6","key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The genotype\u2010tissue expression (GTEx) project","volume":"45","author":"Consortium GT","year":"2013","journal-title":"Nat Genet"},{"issue":"4","key":"e_1_2_8_40_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1046\/j.1524-475X.2003.11402.x","article-title":"Plasminogen activator\/plasmin system: a major player in wound healing?","volume":"11","author":"Li WY","year":"2003","journal-title":"Wound Repair Regen"},{"key":"e_1_2_8_41_1","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/2748340","article-title":"Biophysical mechanisms mediating fibrin fiber lysis","volume":"2017","author":"Hudson NE","year":"2017","journal-title":"Biomed Res Int"},{"issue":"7","key":"e_1_2_8_42_1","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1177\/1753425915589387","article-title":"Peripheral blood neutrophil cytokine hyper\u2010reactivity in chronic periodontitis","volume":"21","author":"Ling MR","year":"2015","journal-title":"Innate Immun"},{"key":"e_1_2_8_43_1","doi-asserted-by":"crossref","DOI":"10.1126\/science.abl5450","article-title":"Fibrin is a critical regulator of neutrophil effector function at the oral mucosal barrier","volume":"374","author":"Silva LM","year":"2021","journal-title":"Science"},{"issue":"20","key":"e_1_2_8_44_1","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1182\/blood-2014-03-560086","article-title":"Genetic variants in PLG, LPA, and SIGLEC 14 as well as smoking contribute to plasma plasminogen levels","volume":"124","author":"Ma Q","year":"2014","journal-title":"Blood"},{"issue":"6","key":"e_1_2_8_45_1","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.jpedsurg.2014.01.034","article-title":"CXCL5 is required for angiogenesis, but not structural adaptation after small bowel resection","volume":"49","author":"Rowland KJ","year":"2014","journal-title":"J Pediatr Surg"},{"issue":"3","key":"e_1_2_8_46_1","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1016\/j.ajpath.2010.11.058","article-title":"Overexpression of CXCL5 is associated with poor survival in patients with pancreatic cancer","volume":"178","author":"Li A","year":"2011","journal-title":"Am J Pathol"},{"issue":"1","key":"e_1_2_8_47_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12933-023-01900-w","article-title":"CXCL5 suppression recovers neovascularization and accelerates wound healing in diabetes mellitus","volume":"22","author":"Chen C","year":"2023","journal-title":"Cardiovasc Diabetol"},{"key":"e_1_2_8_48_1","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1177\/0022034517706311","article-title":"The PF4\/PPBP\/CXCL5 gene cluster is associated with periodontitis","volume":"22","author":"Shusterman A","year":"2017","journal-title":"J Dent Res"},{"issue":"1","key":"e_1_2_8_49_1","first-page":"S237","article-title":"Periodontal manifestations of systemic diseases and developmental and acquired conditions: consensus report of workgroup 3 of the 2017 world workshop on the classification of periodontal and Peri\u2010implant diseases and conditions","volume":"89","author":"Jepsen S","year":"2018","journal-title":"J Periodontol"},{"issue":"20","key":"e_1_2_8_50_1","first-page":"S171","article-title":"Manifestations of systemic diseases and conditions that affect the periodontal attachment apparatus: case definitions and diagnostic considerations","volume":"45","author":"Albandar JM","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"12","key":"e_1_2_8_51_1","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1056\/NEJMoa1612197","article-title":"Interleukin\u201012 and Interleukin\u201023 blockade in leukocyte adhesion deficiency type 1","volume":"376","author":"Moutsopoulos NM","year":"2017","journal-title":"N Engl J Med"},{"key":"e_1_2_8_52_1","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3007696","article-title":"Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL\u201017\u2010driven inflammatory bone loss","volume":"6","author":"Moutsopoulos NM","year":"2014","journal-title":"Sci Transl Med"},{"issue":"2","key":"e_1_2_8_53_1","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1189\/jlb.5A1015-489R","article-title":"Characterization of neutrophil function in Papillon\u2010Lefevre syndrome","volume":"100","author":"Roberts H","year":"2016","journal-title":"J Leukoc Biol"},{"issue":"3","key":"e_1_2_8_54_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000342509","article-title":"Cathepsin C gene 5\u2032\u2010untranslated region mutation in papillon\u2010lefevre syndrome","volume":"225","author":"Kosem R","year":"2012","journal-title":"Dermatology"},{"issue":"10","key":"e_1_2_8_55_1","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.1172\/JCI76009","article-title":"Papillon\u2010Lefevre syndrome patient reveals species\u2010dependent requirements for neutrophil defenses","volume":"124","author":"Sorensen OE","year":"2014","journal-title":"J Clin Invest"},{"issue":"2","key":"e_1_2_8_56_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/ced.12710","article-title":"One mutation, two phenotypes: a single nonsense mutation of the CTSC gene causes two clinically distinct phenotypes","volume":"41","author":"Sulak A","year":"2016","journal-title":"Clin Exp Dermatol"},{"issue":"5","key":"e_1_2_8_57_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/ced.14171","article-title":"Identification of putative genetic modifying factors that influence the development of Papillon\u2010Lefevre or Haim\u2010Munk syndrome phenotypes","volume":"45","author":"Pap EM","year":"2020","journal-title":"Clin Exp Dermatol"},{"issue":"1","key":"e_1_2_8_58_1","first-page":"35","article-title":"Periodontitis in Chediak\u2010Higashi syndrome: an altered Immunoinflammatory response","volume":"3","author":"Thumbigere Math V","year":"2018","journal-title":"JDR Clin Trans Res"},{"issue":"6","key":"e_1_2_8_59_1","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1007\/s10875-011-9572-0","article-title":"Mutations in the ELANE gene are associated with development of periodontitis in patients with severe congenital neutropenia","volume":"31","author":"Ye Y","year":"2011","journal-title":"J Clin Immunol"},{"key":"e_1_2_8_60_1","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2022.972598","article-title":"Case report: five\u2010year periodontal management of a patient with two novel mutation sites in ELANE\u2010induced cyclic neutropenia","volume":"13","author":"Lao Z","year":"2022","journal-title":"Front Genet"},{"issue":"39","key":"e_1_2_8_61_1","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000017372","article-title":"Management of tooth extraction in a patient with ELANE gene mutation\u2010induced cyclic neutropenia: a case report","volume":"98","author":"Aota K","year":"2019","journal-title":"Medicine"},{"issue":"5","key":"e_1_2_8_62_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s10875-007-9106-y","article-title":"The clinical, immunohematological, and molecular study of Iranian patients with severe congenital neutropenia","volume":"27","author":"Rezaei N","year":"2007","journal-title":"J Clin Immunol"},{"issue":"10","key":"e_1_2_8_63_1","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.bbagen.2009.06.004","article-title":"HAX\u20101: a multifunctional protein with emerging roles in human disease","volume":"1790","author":"Fadeel B","year":"2009","journal-title":"Biochim Biophys Acta"},{"issue":"6","key":"e_1_2_8_64_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/j.1651-2227.2007.00274.x","article-title":"Kostmann syndrome or infantile genetic agranulocytosis, part two: understanding the underlying genetic defects in severe congenital neutropenia","volume":"96","author":"Carlsson G","year":"2007","journal-title":"Acta Paediatr"},{"key":"e_1_2_8_65_1","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2017.32","article-title":"Severe congenital neutropenias","volume":"3","author":"Skokowa J","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"5","key":"e_1_2_8_66_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1902\/jop.1997.68.5.473","article-title":"Periodontal findings in Cohen syndrome with chronic neutropenia","volume":"68","author":"Alaluusua S","year":"1997","journal-title":"J Periodontol"},{"issue":"9","key":"e_1_2_8_67_1","article-title":"Cohen syndrome: review of the literature","volume":"10","author":"Rodrigues JM","year":"2018","journal-title":"Cureus"},{"issue":"4","key":"e_1_2_8_68_1","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/jcpe.13940","article-title":"Periodontal disease in patients with WHIM syndrome","volume":"51","author":"Brenchley L","year":"2024","journal-title":"J Clin Periodontol"},{"key":"e_1_2_8_69_1","article-title":"Crosstalk between venous thromboembolism and periodontal diseases: a bioinformatics analysis","volume":"2021","author":"He Z","year":"2021","journal-title":"Dis Markers"},{"issue":"1","key":"e_1_2_8_70_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.24953\/turkjped.2017.01.009","article-title":"Aggressive periodontitis associated with kindler syndrome in a large kindler syndrome pedigree","volume":"59","author":"Yildirim TT","year":"2017","journal-title":"Turk J Pediatr"},{"key":"e_1_2_8_71_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12903-015-0045-3","article-title":"Periodontitis associated with plasminogen deficiency: a case report","volume":"15","author":"Neering SH","year":"2015","journal-title":"BMC Oral Health"},{"key":"e_1_2_8_72_1","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.3389\/fimmu.2019.02962","article-title":"Two different missense C1S mutations, associated to periodontal Ehlers\u2010Danlos syndrome, Lead to identical molecular outcomes","volume":"10","author":"Bally I","year":"2019","journal-title":"Front Immunol"},{"issue":"6","key":"e_1_2_8_73_1","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1007\/s10545-018-0182-3","article-title":"Dental and periodontal manifestations of glycogen storage diseases: a case series of 60 patients","volume":"41","author":"Biosse Duplan M","year":"2018","journal-title":"J Inherit Metab Dis"},{"issue":"25","key":"e_1_2_8_74_1","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.3748\/wjg.v29.i25.3932","article-title":"Glycogen storage diseases: an update","volume":"29","author":"Gumus E","year":"2023","journal-title":"World J Gastroenterol"},{"issue":"12","key":"e_1_2_8_75_1","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1111\/jcpe.13718","article-title":"Oral health status of adult hypophosphatasia patients: a cross\u2010sectional study","volume":"49","author":"Weider M","year":"2022","journal-title":"J Clin Periodontol"},{"issue":"12","key":"e_1_2_8_76_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22126274","article-title":"Genetic susceptibility to periodontal disease in down syndrome: a case\u2010control study","volume":"22","author":"Fernandez M","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"1","key":"e_1_2_8_77_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-12131-7","article-title":"Discovering genetic interactions bridging pathways in genome\u2010wide association studies","volume":"10","author":"Fang G","year":"2019","journal-title":"Nat Commun"},{"issue":"1","key":"e_1_2_8_78_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/jcpe.13712","article-title":"Case\u2010only design identifies interactions of genetic risk variants at SIGLEC5 and PLG with the lncRNA CTD\u20102353F22.1 implying the importance of periodontal wound healing for disease aetiology","volume":"50","author":"Muller R","year":"2023","journal-title":"J Clin Periodontol"},{"key":"e_1_2_8_79_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/jcpe.13712","article-title":"Case\u2010only design identifies interactions of genetic risk variants at SIGLEC5 and PLG with the lncRNA CTD\u20102353F22.1 implying the importance of periodontal wound healing for disease aetiology","volume":"50","author":"Muller R","year":"2022","journal-title":"J Clin Periodontol"},{"issue":"13","key":"e_1_2_8_80_1","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1161\/CIRCULATIONAHA.114.014072","article-title":"ADAMTS\u20107 inhibits re\u2010endothelialization of injured arteries and promotes vascular remodeling through cleavage of thrombospondin\u20101","volume":"131","author":"Kessler T","year":"2015","journal-title":"Circulation"},{"issue":"1","key":"e_1_2_8_81_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-31980-8","article-title":"Genome\u2010wide association meta\u2010analysis of coronary artery disease and periodontitis reveals a novel shared risk locus","volume":"8","author":"Munz M","year":"2018","journal-title":"Sci Rep"},{"issue":"9763","key":"e_1_2_8_82_1","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S0140-6736(10)61996-4","article-title":"Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome\u2010wide association studies","volume":"377","author":"Reilly MP","year":"2011","journal-title":"Lancet"},{"issue":"4","key":"e_1_2_8_83_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/ng.784","article-title":"Large\u2010scale association analysis identifies 13 new susceptibility loci for coronary artery disease","volume":"43","author":"Schunkert H","year":"2011","journal-title":"Nat Genet"},{"issue":"11","key":"e_1_2_8_84_1","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1111\/jcpe.12154","article-title":"Genome\u2010wide association study of chronic periodontitis in a general German population","volume":"40","author":"Teumer A","year":"2013","journal-title":"J Clin Periodontol"},{"issue":"1","key":"e_1_2_8_85_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s13148-021-01190-7","article-title":"Epigenetic adaptations of the masticatory mucosa to periodontal inflammation","volume":"13","author":"Richter GM","year":"2021","journal-title":"Clin Epigenetics"},{"issue":"2","key":"e_1_2_8_86_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1177\/00220345211029266","article-title":"Exome sequencing of 5 families with severe early\u2010onset periodontitis","volume":"101","author":"Richter GM","year":"2022","journal-title":"J Dent Res"},{"key":"e_1_2_8_87_1","first-page":"93","article-title":"BACH1 binding links the genetic risk for severe periodontitis with ST8SIA1","volume":"22","author":"Chopra A","year":"2021","journal-title":"J Dent Res"},{"key":"e_1_2_8_88_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.lfs.2018.04.017","article-title":"Slit2\u2010Robo2 signaling modulates the fibrogenic activity and migration of hepatic stellate cells","volume":"203","author":"Zeng Z","year":"2018","journal-title":"Life Sci"},{"issue":"1","key":"e_1_2_8_89_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-56137-z","article-title":"JNK\u2010mediated Slit\u2010Robo signaling facilitates epithelial wound repair by extruding dying cells","volume":"9","author":"Iida C","year":"2019","journal-title":"Sci Rep"},{"issue":"1","key":"e_1_2_8_90_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/00041433-200502000-00005","article-title":"ATP\u2010binding cassette transporter AI and its role in HDL formation","volume":"16","author":"Lee JY","year":"2005","journal-title":"Curr Opin Lipidol"},{"issue":"7","key":"e_1_2_8_91_1","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1161\/ATVBAHA.114.304959","article-title":"Increased systemic and plaque inflammation in ABCA1 mutation carriers with attenuation by statins","volume":"35","author":"Bochem AE","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"3","key":"e_1_2_8_92_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1080\/09168451.2018.1547105","article-title":"Cell migration is negatively modulated by ABCA1","volume":"83","author":"Ito S","year":"2019","journal-title":"Biosci Biotechnol Biochem"},{"issue":"12","key":"e_1_2_8_93_1","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1177\/0022034519875443","article-title":"Smoking modifies the genetic risk for early\u2010onset periodontitis","volume":"98","author":"Freitag\u2010Wolf S","year":"2019","journal-title":"J Dent Res"},{"issue":"22","key":"e_1_2_8_94_1","doi-asserted-by":"crossref","DOI":"10.1016\/S0021-9258(17)40773-3","article-title":"Expression cloning of a GM3\u2010specific alpha\u20102,8\u2010sialyltransferase (GD3 synthase)","volume":"269","author":"Sasaki K","year":"1994","journal-title":"J Biol Chem"},{"issue":"35","key":"e_1_2_8_95_1","doi-asserted-by":"crossref","first-page":"27213","DOI":"10.1074\/jbc.M109.087791","article-title":"Ganglioside GD3 enhances adhesion signals and augments malignant properties of melanoma cells by recruiting integrins to glycolipid\u2010enriched microdomains","volume":"285","author":"Ohkawa Y","year":"2010","journal-title":"J Biol Chem"},{"issue":"6","key":"e_1_2_8_96_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00335-008-9113-1","article-title":"The collaborative cross, developing a resource for mammalian systems genetics: a status report of the Wellcome Trust cohort","volume":"19","author":"Iraqi FA","year":"2008","journal-title":"Mamm Genome"},{"key":"e_1_2_8_97_1","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1093\/hmg\/ddt065","article-title":"Exploring the genetic basis of chronic periodontitis: a genome\u2010wide association study","volume":"22","author":"Divaris K","year":"2013","journal-title":"Hum Mol Genet"},{"issue":"3","key":"e_1_2_8_98_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1055\/s-2004-831051","article-title":"Platelet factor 4: an inhibitor of angiogenesis","volume":"30","author":"Bikfalvi A","year":"2004","journal-title":"Semin Thromb Hemost"},{"issue":"5","key":"e_1_2_8_99_1","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.4049\/jimmunol.174.5.2680","article-title":"Platelet factor 4 differentially modulates CD4+CD25+ (regulatory) versus CD4+CD25\u2010 (nonregulatory) T cells","volume":"174","author":"Liu CY","year":"2005","journal-title":"J Immunol"},{"issue":"10","key":"e_1_2_8_100_1","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1177\/154405910808701017","article-title":"Cathepsin C gene variants in aggressive periodontitis","volume":"87","author":"Noack B","year":"2008","journal-title":"J Dent Res"},{"issue":"3","key":"e_1_2_8_101_1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/humu.10314","article-title":"The role of cathepsin C in Papillon\u2010Lefevre syndrome, prepubertal periodontitis, and aggressive periodontitis","volume":"23","author":"Hewitt C","year":"2004","journal-title":"Hum Mutat"},{"issue":"5","key":"e_1_2_8_102_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/humu.9243","article-title":"Loss\u2010of\u2010function mutations in cathepsin C in two families with Papillon\u2010Lefevre syndrome are associated with deficiency of serine proteinases in PMNs","volume":"23","author":"Haar SF","year":"2004","journal-title":"Hum Mutat"},{"issue":"2","key":"e_1_2_8_103_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1600-0722.2006.00344.x","article-title":"Structure of the periodontium in cathepsin C\u2010deficient mice","volume":"114","author":"Haar SF","year":"2006","journal-title":"Eur J Oral Sci"},{"issue":"9","key":"e_1_2_8_104_1","doi-asserted-by":"crossref","first-page":"5284","DOI":"10.1128\/IAI.02016-05","article-title":"Role of polymorphonuclear leukocyte\u2010derived serine proteinases in defense against Actinobacillus actinomycetemcomitans","volume":"74","author":"Haar SF","year":"2006","journal-title":"Infect Immun"},{"key":"e_1_2_8_105_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1600-0757.2007.00233.x","article-title":"Mendelian forms of periodontitis","volume":"45","author":"Hart TC","year":"2007","journal-title":"Periodontol 2000"},{"issue":"1","key":"e_1_2_8_106_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/imr.13152","article-title":"Neutrophils in the periodontium: interactions with pathogens and roles in tissue homeostasis and inflammation","volume":"314","author":"Uriarte SM","year":"2023","journal-title":"Immunol Rev"},{"issue":"1","key":"e_1_2_8_107_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1182\/asheducation-2017.1.187","article-title":"Non\u2010chemotherapy drug\u2010induced neutropenia: key points to manage the challenges","volume":"2017","author":"Curtis BR","year":"2017","journal-title":"Hematology Am Soc Hematol Educ Program"},{"issue":"1","key":"e_1_2_8_108_1","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1111\/imr.12724","article-title":"Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis","volume":"287","author":"Silva LM","year":"2019","journal-title":"Immunol Rev"},{"issue":"4","key":"e_1_2_8_109_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/70525","article-title":"Loss\u2010of\u2010function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis","volume":"23","author":"Toomes C","year":"1999","journal-title":"Nat Genet"},{"issue":"17","key":"e_1_2_8_110_1","doi-asserted-by":"crossref","DOI":"10.1074\/jbc.M500340200","article-title":"Proteolysis of macrophage inflammatory protein\u20101alpha isoforms LD78beta and LD78alpha by neutrophil\u2010derived serine proteases","volume":"280","author":"Ryu OH","year":"2005","journal-title":"J Biol Chem"},{"issue":"3","key":"e_1_2_8_111_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/jlb.61.3.361","article-title":"Human neutrophil elastase abolishes interleukin\u20108 chemotactic activity","volume":"61","author":"Leavell KJ","year":"1997","journal-title":"J Leukoc Biol"},{"issue":"1","key":"e_1_2_8_112_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/imr.13171","article-title":"Neutrophils are gatekeepers of mucosal immunity","volume":"314","author":"Silva LM","year":"2023","journal-title":"Immunol Rev"},{"key":"e_1_2_8_113_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1046\/j.0906-6713.2003.03207.x","article-title":"Systemic disease and periodontitis: manifestations of neutrophil dysfunction","volume":"32","author":"Deas DE","year":"2003","journal-title":"Periodontol 2000"},{"issue":"3","key":"e_1_2_8_114_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004698","article-title":"Subgingival microbial communities in leukocyte adhesion deficiency and their relationship with local immunopathology","volume":"11","author":"Moutsopoulos NM","year":"2015","journal-title":"PLoS Pathog"},{"issue":"5","key":"e_1_2_8_115_1","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1002\/JLB.5HI0420-648R","article-title":"Frontline science: activation of metabolic nuclear receptors restores periodontal tissue homeostasis in mice with leukocyte adhesion deficiency\u20101","volume":"108","author":"Kajikawa T","year":"2020","journal-title":"J Leukoc Biol"},{"issue":"3","key":"e_1_2_8_116_1","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1182\/blood.V90.3.958","article-title":"Homozygous mutations in the plasminogen gene of two unrelated girls with ligneous conjunctivitis","volume":"90","author":"Schuster V","year":"1997","journal-title":"Blood"},{"issue":"2","key":"e_1_2_8_117_1","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1160\/TH04-01-0041","article-title":"Characterization of plasminogen variants in healthy subjects and plasminogen mutants in patients with inherited plasminogen deficiency by isoelectric focusing gel electrophoresis","volume":"92","author":"Tefs K","year":"2004","journal-title":"Thromb Haemost"},{"issue":"9","key":"e_1_2_8_118_1","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1177\/00220345231171837","article-title":"Plasmin\u2010mediated fibrinolysis in periodontitis pathogenesis","volume":"102","author":"Silva LM","year":"2023","journal-title":"J Dent Res"},{"issue":"5","key":"e_1_2_8_119_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.ajhg.2016.08.019","article-title":"Periodontal Ehlers\u2010Danlos syndrome is caused by mutations in C1R and C1S, which encode subcomponents C1r and C1s of complement","volume":"99","author":"Kapferer\u2010Seebacher I","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"12","key":"e_1_2_8_120_1","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1111\/jcpe.13698","article-title":"Oral characteristics in adult individuals with periodontal Ehlers\u2010Danlos syndrome","volume":"49","author":"Lepperdinger U","year":"2022","journal-title":"J Clin Periodontol"},{"issue":"14","key":"e_1_2_8_121_1","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1016\/j.cell.2024.05.003","article-title":"Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss","volume":"187","author":"Wang H","year":"2024","journal-title":"Cell"},{"issue":"26","key":"e_1_2_8_122_1","article-title":"Microbiome\u2010associated human genetic variants impact phenome\u2010wide disease risk","volume":"119","author":"Markowitz RHG","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"e_1_2_8_123_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/s41588-021-00991-z","article-title":"Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort","volume":"54","author":"Qin Y","year":"2022","journal-title":"Nat Genet"},{"issue":"2","key":"e_1_2_8_124_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41588-021-00992-y","article-title":"Effect of host genetics on the gut microbiome in 7738 participants of the Dutch microbiome project","volume":"54","author":"Lopera\u2010Maya EA","year":"2022","journal-title":"Nat Genet"},{"issue":"7","key":"e_1_2_8_125_1","doi-asserted-by":"crossref","first-page":"21S","DOI":"10.1177\/0022034512447951","article-title":"Genome\u2010wide association study of periodontal pathogen colonization","volume":"91","author":"Divaris K","year":"2012","journal-title":"J Dent Res"},{"issue":"2","key":"e_1_2_8_126_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41588-018-0309-3","article-title":"Genome\u2010wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences","volume":"51","author":"Karlsson Linner R","year":"2019","journal-title":"Nat Genet"},{"issue":"2","key":"e_1_2_8_127_1","doi-asserted-by":"crossref","first-page":"R133","DOI":"10.1093\/hmg\/ddz187","article-title":"Towards clinical utility of polygenic risk scores","volume":"28","author":"Lambert SA","year":"2019","journal-title":"Hum Mol Genet"},{"issue":"1","key":"e_1_2_8_128_1","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1038\/s41467-021-22491-8","article-title":"Common variants in Alzheimer's disease and risk stratification by polygenic risk scores","volume":"12","author":"Rojas I","year":"2021","journal-title":"Nat Commun"}],"container-title":["Periodontology 2000"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/prd.12622","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T05:46:28Z","timestamp":1739598388000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/prd.12622"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,14]]},"references-count":127,"alternative-id":["10.1111\/prd.12622"],"URL":"https:\/\/doi.org\/10.1111\/prd.12622","archive":["Portico"],"relation":{},"ISSN":["0906-6713","1600-0757"],"issn-type":[{"value":"0906-6713","type":"print"},{"value":"1600-0757","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,14]]},"assertion":[{"value":"2024-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"prd.12622"}}