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We investigated the genetic basis of host antibody responses against these species through a genome-wide association study (GWAS) to identify the genetic determinants of this immune reactivity. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG) antibody levels against\n                    <jats:italic toggle=\"yes\">A. actinomycetemcomitans<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">P. gingivalis<\/jats:italic>\n                    were determined using multiserotype enzyme-linked immunosorbent assay in 3,719 participants from 4 Finnish cohort studies: FinnTwin, Parogene, FINRISK97, and Health-2000. The associations of genetic polymorphisms and imputed human leukocyte antigen (HLA) alleles with antibody levels were investigated. All antibody levels presented significant increasing trends with periodontitis stage and grade.\n                    <jats:italic toggle=\"yes\">A. actinomycetemcomitans<\/jats:italic>\n                    IgG displayed association with single nucleotide polymorphisms (SNPs) in chromosome 6 with lead SNP rs574581129 (near\n                    <jats:italic toggle=\"yes\">HLA-DRB1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009=\u20093.6 \u00d7 10\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) and\n                    <jats:italic toggle=\"yes\">P. gingivalis<\/jats:italic>\n                    IgG in chromosome 14 with lead SNP rs146761521 (near\n                    <jats:italic toggle=\"yes\">NUBPL<\/jats:italic>\n                    , 5.5 \u00d7 10\n                    <jats:sup>\u22128<\/jats:sup>\n                    ). In addition, all antibody levels presented suggestive associations with several loci. Detailed HLA analyses revealed that\n                    <jats:italic toggle=\"yes\">A. actinomycetemcomitans<\/jats:italic>\n                    IgG was associated with DQA1*01:01, DQB1*05:01, and DRB1*01:01 and\n                    <jats:italic toggle=\"yes\">P. gingivalis<\/jats:italic>\n                    IgG with HLA-A*02:01 alleles. Both IgA and IgG antibody levels against microbial biomarker species of periodontitis increase with periodontitis stage and grade, but genetic variation is also a significant predictor. Specific alleles within the HLA region may influence antibody responses to\n                    <jats:italic toggle=\"yes\">A. actinomycetemcomitans<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">P. gingivalis<\/jats:italic>\n                    , highlighting potential genetic contributions to the immunological mechanisms underlying periodontitis.\n                  <\/jats:p>","DOI":"10.1177\/00220345251387642","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T05:39:27Z","timestamp":1764567567000},"page":"866-874","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["GWAS of Serum Antibodies to Microbial Biomarker Species of Periodontitis"],"prefix":"10.1177","volume":"105","author":[{"given":"H.","family":"Abdelkader","sequence":"first","affiliation":[{"name":"School of Medicine, Institute of Dentistry, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7576-090X","authenticated-orcid":false,"given":"A.","family":"Salminen","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9670-339X","authenticated-orcid":false,"given":"J.","family":"Leskel\u00e4","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Palviainen","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Salasuo","sequence":"additional","affiliation":[{"name":"School of Medicine, Institute of Dentistry, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Paju","sequence":"additional","affiliation":[{"name":"School of Medicine, Institute of Dentistry, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"M\u00e4ntyl\u00e4","sequence":"additional","affiliation":[{"name":"School of Medicine, Institute of Dentistry, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Suominen","sequence":"additional","affiliation":[{"name":"School of Medicine, Institute of Dentistry, University of Eastern Finland, Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Kaprio","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Salomaa","sequence":"additional","affiliation":[{"name":"Finnish Institute for Health and Welfare (THL), Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Sinisalo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3563-1876","authenticated-orcid":false,"given":"P.J.","family":"Pussinen","sequence":"additional","affiliation":[{"name":"School of Medicine, Institute of Dentistry, University of Eastern Finland, Kuopio, Finland"},{"name":"Oral and Maxillofacial Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Behle JH Sedaghatfar MG Demmer RT Wolf DL Celenti R Kebschull M Belusko PB Herrera-Abreu M Lalla E Papapanou PN. 2009. 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