{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:11:17Z","timestamp":1793833877929,"version":"4.6.1"},"update-to":[{"DOI":"10.12688\/f1000research.151954.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000}}],"reference-count":41,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Aims To study the association between AIM2 gene polymorphisms and the tendency for periodontal infection and coronary heart disease, and to determine whether males or females are more susceptible to these diseases. Additionally, we examined its association with the features of periodontal disease. Methods 140 patients were enrolled in this study, and those who took part were divided into four groups as follows: healthy (c), periodontal disease (P), coronary heart disease with intact periodontium (AS-C), and coronary heart disease with periodontal disease (AS-P). Information on entrants, including age ranging from 40 to 70 years old, sex of both males and females who fulfilled the study\u2019s criteria, body mass index with ordinary rang less than 30 kg\/m\n                    <ns3:sup>2<\/ns3:sup>\n                    , socioeconomic status, tooth brushing frequency at least two times per- day, and indicators of periodontal disease severity, was documented. Blood samples were collected, and AIM2 gene polymorphisms were evaluated by polymerase chain reaction test, gel phase, and sequences. Results Genetic analysis of AIM2 G\/T (rs\n                    <ns3:italic>2793845<\/ns3:italic>\n                    ) revealed a high frequency of the (T) allele and (GT and TT) genotypes that were detected in the periodontal disease and coronary heart disease groups in males. The Hardy-Weinberg equilibrium of alleles and genotypes did not differ significantly (p &gt; 0.05) between the study groups. Gene polymorphisms were also significantly (p \u2264 0.05) correlated with indicators of periodontal disease severity. Conclusion High frequenting of (T) alleles and (GT, TT) genotypes in AIM2 single nucleotide polymorphisms (SNP) were associated with an increased tendency to develop periodontal disease and coronary heart disease. It can be supposed that it has a causative function in the pathophysiology of both disorders, and the validity of SNP as a potential genomic factor for the risk of both disorders in Iraqi males.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.151954.2","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T14:35:07Z","timestamp":1752503707000},"page":"810","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Absent in Melanoma 2 Gene Associated Periodontitis and Coronary Heart Disease"],"prefix":"10.12688","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8189-1801","authenticated-orcid":false,"given":"Zina Ali","family":"Daily","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Batool Hassan","family":"Al-Ghurabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"107-124","DOI":"10.1111\/prd.12299","article-title":"Periodontal therapy and cardiovascular risk.","volume":"83","author":"M Orlandi","year":"2020","journal-title":"Periodontology."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"135-142","DOI":"10.1590\/0103-6440202002561","article-title":"In Vitro Homeostasis of Rat Oral Epithelial Cell Cultures Following Withdrawal of Periodontal Pathogens.","volume":"31","author":"A Abdulkareem","year":"2020","journal-title":"Braz. Dent. J."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"37-68","DOI":"10.1111\/j.1600-0757.2011.00415.x","article-title":"Genetic susceptibility to periodontitis.","volume":"58","author":"M Laine","year":"2021","journal-title":"J. Periodontol. 2000."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"66-89","DOI":"10.1111\/prd.12302","article-title":"Periodontal diseases and association with atherosclerotic Disease.","volume":"83","author":"D Herrera","year":"2020","journal-title":"Periodontology."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"268-278","DOI":"10.1016\/j.jdsr.2022.09.001","article-title":"Pathogenesis of periodontitis-A potential role for epithelial mesenchymal transition.","volume":"58","author":"S Saliem","year":"2022","journal-title":"Jpn. Dent. Sci. Rev. J."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"522-531","DOI":"10.26655\/JMCHEMSCI.2023.3.9","article-title":"Potential Role of NLRP3 Inflammasome Activation in the Pathogenesis of Periodontitis Patients with Type 2 Diabetes Mellitus.","volume":"6","author":"M Al-Obaidi","year":"2023","journal-title":"J. Med. Chem. Sci."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"493-501","DOI":"10.1902\/jop.2016.160279","article-title":"Effect of non-surgical periodontal treatment on gingival crevicular fluid and serum endocan, vascular endothelial growth factor-A, and tumor necrosis factor-alpha levels.","volume":"88","author":"C Turer","year":"2017","journal-title":"J. Periodontol."},{"key":"ref8","first-page":"37-39","article-title":"The Role of Soluble TLR-2 in the Immunopathogenesis of Gingivitis.","volume":"28","author":"B Al-Ghurabi","year":"2021","journal-title":"Intern. Med."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"91-106","DOI":"10.1002\/ctm2.13","article-title":"NLRP3 inflammasome, an immune-inflammatory target in pathogenesis and treatment of cardiovascular diseases.","volume":"10","author":"Y Wang","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1742-1756","DOI":"10.1093\/eurheartj\/ehab107","article-title":"Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality.","volume":"42","author":"S Schunk","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"929162","DOI":"10.3389\/fgene.2022.929162","article-title":"Roles of AIM2 Gene and AIM2 Inflammasome in the Pathogenesis and Treatment of Psoriasis.","volume":"13","author":"J Wang","year":"2022","journal-title":"J. Front. Genet."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"S159-s172","DOI":"10.1002\/JPER.18-0006","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition.","volume":"89","author":"M Tonetti","year":"2018","journal-title":"J. Periodontol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"S68-S77","DOI":"10.1111\/jcpe.12940","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-Implant Diseases and Conditions.","volume":"45","author":"I Chapple","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1902\/jop.1972.43.1.38","article-title":"The plaque control record.","volume":"43","author":"T O\u2019Leary","year":"1972","journal-title":"J. Periodontol."},{"key":"ref15","first-page":"107-113","article-title":"Gingival sulcus bleeding--a leading symptom in initial gingivitis.","volume":"15","author":"H M\u00fchlemann","year":"1971","journal-title":"Helv. Odontol. Acta."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"78-83","DOI":"10.1055\/s-0041-1732954","article-title":"Assessment of Serum Interleukin-1\u03b2 and Interleukin-6 Levels in Patients with Chronic Periodontitis and Coronary Heart Disease.","volume":"10","author":"F Al-Taweel","year":"2021","journal-title":"Eur. J. Gen. Dent."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"756-765","DOI":"10.1002\/JPER.18-0466","article-title":"Dysregulation Of miR-146a by Periodontal Pathogens: a risk for Acute Coronary Syndrome.","volume":"90","author":"B Gita","year":"2019","journal-title":"J. Periodontol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e12442","DOI":"10.1111\/jicd.12442","article-title":"The Periodontal-Cardiovascular alliance: Evaluation of miRNA-146a in subgingival plaque samples of chronicperiodontitis patients with and without coronary heart disease.","volume":"10","author":"K Yagnik","year":"2019","journal-title":"J. Investig. Clin. Dent."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e20170322","DOI":"10.1590\/1678-7757-2017-0322","article-title":"Circulation levels of acute phase proteins pentraxin 3 and serum amyloid A in atherosclerosis have correlations with periodontal inflamed surface area.","volume":"26","author":"B Temelli","year":"2018","journal-title":"J. Appl. Oral Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.3390\/diagnostics12102485","article-title":"Determination of the accuracy of salivary biomarkers for periodontal diagnosis.","volume":"12","author":"H Mohammed","year":"2022","journal-title":"Diagnostics."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"663-672","DOI":"10.1902\/jop.2017.160553","article-title":"Common polymorphisms in the IFI16 and AIM2 genes are associated with periodontal disease.","volume":"88","author":"J Marchesan","year":"2017","journal-title":"J. Periodontol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"604975","DOI":"10.3389\/fimmu.2021.604975","article-title":"Single-Nucleotide Variants in the AIM2 \u2013 Absent in Melanoma 2 Gene (rs1103577) Associated with Protection for Tuberculosis.","volume":"12","author":"M Figueira","year":"2021","journal-title":"J. Front. Immunol."},{"key":"ref24","first-page":"164-169","article-title":"Study the role of proinflammatory and anti-inflammatory cytokines in patients with chronic periodontitis in Iraqi.","volume":"24","author":"Z Shaker","year":"2012","journal-title":"J. Bagh. College Dentistry."},{"key":"ref25","first-page":"161-165","article-title":"Evaluation of serum anticardiolipin antibody, hs-CRP, and IL-6 levels in chronic periodontitis as possible risk factors for cardiovascular diseases.","volume":"24","author":"B Al-Ghurabei","year":"2012","journal-title":"J. Bagh. College Dentistry."},{"key":"ref26","first-page":"181-186","article-title":"Nuclear factor-kappa B gene Polymorphism and Interleukin-8 in Iraqi population with severe chronic periodontitis.","volume":"11","author":"R Fadhil","year":"2019","journal-title":"J. Glob. Pharma Technol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"65-69","DOI":"10.26477\/jbcd.v31i2.2626","article-title":"This retrospective study investigated the consistency between reported chief complaint and periodontal health status of Iraqi patients in relation to age and gender (A retrospective study).","volume":"31","author":"A Abdulkareem","year":"2019","journal-title":"J. Bagh. College Dentistry."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"S62-S72","DOI":"10.1016\/j.jcmg.2012.02.003","article-title":"Gender and the extent of coronary atherosclerosis, plaque composition, and clinical outcomes in acute coronary syndromes.","volume":"5","author":"A Lansky","year":"2012","journal-title":"J. Am. Coll. Cardiol. Img."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1186\/s12903-023-03584-w","article-title":"MicroRNA-155 (miR-155) as an accurate biomarker of periodontal status and coronary heart disease severity: a case\u2013control study.","volume":"23","author":"Z Daily","year":"2023","journal-title":"J. BMC Oral Health."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"610-617","DOI":"10.1177\/0022034517699786","article-title":"Genetic susceptibility contributing to periodontal and cardiovascular disease.","volume":"96","author":"G Aarabi","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"13678","DOI":"10.1038\/s41598-018-31980-8","article-title":"Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus.","volume":"8","author":"M Munz","year":"2018","journal-title":"Sci. Rep."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"159-167","DOI":"10.1161\/CIRCGENETICS.114.000554","article-title":"Genetic evidence for plasminogen as a shared genetic risk factor of coronary artery disease and periodontitis.","volume":"8","author":"A Schaefer","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e1000378","DOI":"10.1371\/journal.pgen.1000378","article-title":"Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis.","volume":"5","author":"A Schaefer","year":"2009","journal-title":"PLoS Genet."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"381-385","DOI":"10.1038\/sj.bdj.2017.224","article-title":"Evidence summary: the relationship between oral and cardiovascular disease.","volume":"222","author":"T Dietrich","year":"2017","journal-title":"Br. Dent. J."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"59-68","DOI":"10.1016\/j.amjcard.2009.05.002","article-title":"The American Journal of Cardiology and Journal of Periodontology Editors\u2019 Consensus: periodontitis and atherosclerotic cardiovascular disease.","volume":"104","author":"V Friedewald","year":"2009","journal-title":"Am. J. Cardiol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"315-321","DOI":"10.1016\/j.tem.2015.03.001","article-title":"Oral infections and cardiovascular disease.","volume":"26","author":"K Kholy","year":"2015","journal-title":"Trends Endocrinol. Metab."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"2520-2544","DOI":"10.1161\/CIR.0b013e31825719f3","article-title":"Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association? a scientific statement from the American Heart Association.","volume":"125","author":"P Lockhart","year":"2012","journal-title":"Circulation."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"S51-S69","DOI":"10.1111\/jcpe.12060","article-title":"Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases.","volume":"40","author":"H Schenkein","year":"2013","journal-title":"J. Clin. Periodontol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"80-89","DOI":"10.1038\/s41431-018-0210-7","article-title":"Linear isoforms of the long noncoding RNA CDKN2B-AS1 regulate the c-myc-enhancer binding factor RBMS1.","volume":"27","author":"M Hubberten","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"4516-4527","DOI":"10.1093\/hmg\/ddt299","article-title":"The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer regulates ADIPOR1, VAMP3 and C11ORF10.","volume":"22","author":"G Bochenek","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.24017892.v2","article-title":"Data=Zina Ali-Res=F1000 Research, version 2.","author":"Z Daily","year":"2023","journal-title":"Figshare."},{"key":"ref42","article-title":"zina ali-res (1).xlsx (20.42 kB).","author":"Z Daily","year":"2023","journal-title":"Figshare."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/13-810\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-810\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/13-810\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T19:35:12Z","timestamp":1763667312000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/13-810\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":41,"URL":"https:\/\/doi.org\/10.12688\/f1000research.151954.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.151954.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.184412.r398472","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.184412.r412798","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.184412.r398472","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.184412.r412798","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/13-810\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.184412.r398472, Athraa Ali Mahmood, Department of Oral Surgery and Periodontics, Mustansiriyah University, Baghdad, 13 Aug 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-810\/v2#referee-response-398472","order":0,"name":"referee-response-398472","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.166650.r304567, Paras Ahmad, College of Dentistry, University of Saskatchewan, Saskatoon, Saskatchewan, 30 Jul 2024, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/f1000research.com\/articles\/13-810\/v1#referee-response-304567","order":1,"name":"referee-response-304567","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Zina Daily<\/b>; \n<i>Posted: 05 Jul 2025<\/i>; Thank you for your letter and for the reviewer\u2019 comments concerning our manuscript. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our research. We have studied comments carefully and have made correction which we hope meet with approval. \n<b>Response to comment of reviewer2<\/b> 1.Response to comment: 1- It is not clear how well the control group (healthy participants) is matched with the other groups in terms of age, gender, and other potential confounding factors. Proper matching is crucial to ensure that differences observed are due to the variables of interest (AIM2 gene polymorphisms) rather than other extraneous variables. Response: Thank you for your suggestion. I agree that the information of control group (healthy participants) and the other groups in terms of age, gender, and other potential confounding factors are due to the variables of interest (AIM2 gene polymorphisms), so that we matched the same range of subjects to avoid bias of the study and focusing on one variable (genetic changes) effecting and inflammatory process. We added the socioeconomic status, tooth brushing frequency at least two times per- day in the variable because these were recorded during data collection. 2.Response to comment: 2-The clinical assessments of periodontal disease indicators and CHD diagnosis involve subjective components and specialist interpretations. There could be variability in these assessments, and the study does not mention blinding of assessors, which could introduce bias. Response: Thank you for pointing that out. We measured standardized periodontal clinical indicators to detect healthy periodontium and periodontal disease, while specialist of cardiology is blinding to subjects of CHD patients that related to CHD with periodontitis group or CHD with healthy periodontium group. As well as, the blind laboratory doctor collected, process blood samples and detected gene polymorphism. The statistic of data process by blind analyzer. We will revise the material and methods (Sample) to make this part clearer and more explicit. 3.Response to comment: 3-The study relies on one-way ANOVA and Odds\/Ratios without detailed reporting of how these analyses were conducted, including handling potential confounders. Additionally, the use of Pearson correlation coefficients for genetic polymorphism analysis might not be the most appropriate method, given the typically non-linear relationships and categorical nature of genetic data. Response Thank you for your question. I was adding detailed reporting of how these analyses were conducted in revision. Additionally, the use of multiple logistic regression for analysis the association of AIM2 gene polymorphism with susceptibility to periodontitis and CHD in Table 5. 4- Response to comment: 4-While the study attempts to control for some confounders by excluding certain participants, it does not appear to account for other potential confounders, such as socioeconomic status, diet, and oral hygiene practices, which could influence both periodontal health and CHD. Response: Thank you for your question. I was adding the account for other potential confounders, such as socioeconomic status, and oral hygiene practices in the new revision, which could influence both periodontal health and CHD in table 1. 5- Response to comment: 5-The focus on a single gene polymorphism (AIM2 G\/T rs2793845) might be too narrow, as complex diseases like periodontal disease and CHD are often influenced by multiple genetic and environmental factors. Additionally, the study does not discuss the functional implications of this polymorphism or its interaction with other genetic factors. Response: Thank you for your question. In our study, we examined Iraqi subjects concerning the SNPs of AIM2 gene which detected the only single nucleotide polymorphism in Aim2 gene at location rs2793845. It was a significant difference between healthy individuals, periodontal disease and CHD in the examined groups of Iraqi subjects. Furthermore, the functional implications of this polymorphism were added and explained in discussion part. 6- Response to comment: 6-The study design is cross-sectional, limiting the ability to infer causation or understand the temporal relationship between AIM2 polymorphisms, periodontal disease, and CHD. Longitudinal studies would be more informative in establishing these relationships. Response\uff1a Thank you for this suggestion. The longitudinal studies would be more informative in establishing these relationships, but it required more time and costly. Thus, further and longitudinal studies are essential to investigate and explore the function of AIM2 gene polymorphisms as the prognostic and therapeutic implications in the progression of periodontal disease and CHD.","URL":"https:\/\/f1000research.com\/articles\/13-810\/v2#referee-comment-14200","order":2,"name":"referee-comment-14200","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.184412.r412798, Snophia Suresh, Thai Moogambigai Dental College and Hospital, Chennai, Tamilnadu, 23 Oct 2025, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/13-810\/v2#referee-response-412798","order":3,"name":"referee-response-412798","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}