The Novel ASIC2 Locus is Associated with Severe Gingival Inflammation
An increasing body of evidence suggests a significant genetic regulation of inflammatory response mechanisms; however, little is known regarding the genetic determinants of severe gingival inflammation (GI). We conducted a genome-wide association study of severe GI among 4077 European American adult...
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Published in | JDR clinical and translational research Vol. 1; no. 2; p. 163 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
01.07.2016
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Abstract | An increasing body of evidence suggests a significant genetic regulation of inflammatory response mechanisms; however, little is known regarding the genetic determinants of severe gingival inflammation (GI). We conducted a genome-wide association study of severe GI among 4077 European American adults, participants in the Dental Atherosclerosis Risk In Communities cohort. The severe GI trait was defined dichotomously using the 90
percentile of gingival index ≥2 extent score. Genotyping was performed with the Affymetrix 6.0 array platform and an imputed set of 2.5 million markers, based on HapMap Phase II CEU build 36, was interrogated. Genetic models were based on logistic regression and controlled for ancestry (10 principal components), sex, age, and examination center. One locus on chromosome 17 met genome-wide statistical significance criteria-lead single nucleotide polymorphism (SNP): rs11652874 [minor allele frequency=0.06, intronic to
(acid sensing ionic channel-2, formerly named
); odds ratio=2.1, 95% confidence interval=1.6-2.7, p=3.9×10
]. This association persisted among subjects with severe periodontitis and was robust to adjustment for microbial plaque index. Moreover, the minor [G] allele was associated with higher levels of severe GI in stratified analyses among subsets of participants with high load of either "red" or "orange" complex pathogens, although this association was not statistically significant. While these results will require replication in independent samples and confirmation by mechanistic studies, this locus appears as a promising candidate for severe gingival inflammation. Our findings suggest that genetic variation in
is significantly associated with severe gingival inflammation and the association is plaque-independent. |
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AbstractList | An increasing body of evidence suggests a significant genetic regulation of inflammatory response mechanisms; however, little is known regarding the genetic determinants of severe gingival inflammation (GI). We conducted a genome-wide association study of severe GI among 4077 European American adults, participants in the Dental Atherosclerosis Risk In Communities cohort. The severe GI trait was defined dichotomously using the 90
percentile of gingival index ≥2 extent score. Genotyping was performed with the Affymetrix 6.0 array platform and an imputed set of 2.5 million markers, based on HapMap Phase II CEU build 36, was interrogated. Genetic models were based on logistic regression and controlled for ancestry (10 principal components), sex, age, and examination center. One locus on chromosome 17 met genome-wide statistical significance criteria-lead single nucleotide polymorphism (SNP): rs11652874 [minor allele frequency=0.06, intronic to
(acid sensing ionic channel-2, formerly named
); odds ratio=2.1, 95% confidence interval=1.6-2.7, p=3.9×10
]. This association persisted among subjects with severe periodontitis and was robust to adjustment for microbial plaque index. Moreover, the minor [G] allele was associated with higher levels of severe GI in stratified analyses among subsets of participants with high load of either "red" or "orange" complex pathogens, although this association was not statistically significant. While these results will require replication in independent samples and confirmation by mechanistic studies, this locus appears as a promising candidate for severe gingival inflammation. Our findings suggest that genetic variation in
is significantly associated with severe gingival inflammation and the association is plaque-independent. |
Author | Kim, Steven J Morelli, Thiago Barros, Silvana North, Kari E Wu, Di Moss, Kevin Divaris, Kimon Marchesan, Julie Beck, James Offenbacher, Steven Yu, Ning Zhang, Shaoping Agler, Cary |
Author_xml | – sequence: 1 givenname: Shaoping surname: Zhang fullname: Zhang, Shaoping organization: Center for Oral and Systemic Disease, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 2 givenname: Kimon surname: Divaris fullname: Divaris, Kimon organization: Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill – sequence: 3 givenname: Kevin surname: Moss fullname: Moss, Kevin organization: Center for Oral and Systemic Disease, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 4 givenname: Ning surname: Yu fullname: Yu, Ning organization: Center for Oral and Systemic Disease, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 5 givenname: Silvana surname: Barros fullname: Barros, Silvana organization: Center for Oral and Systemic Disease, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 6 givenname: Julie surname: Marchesan fullname: Marchesan, Julie organization: Center for Oral and Systemic Disease, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 7 givenname: Thiago surname: Morelli fullname: Morelli, Thiago organization: Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 8 givenname: Cary surname: Agler fullname: Agler, Cary organization: Center for Oral & Craniofacial Health Sciences, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 9 givenname: Steven J surname: Kim fullname: Kim, Steven J organization: Center for Oral and Systemic Disease, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 10 givenname: Di surname: Wu fullname: Wu, Di organization: Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 11 givenname: Kari E surname: North fullname: North, Kari E organization: Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill Gillings School of Global Public Health – sequence: 12 givenname: James surname: Beck fullname: Beck, James organization: Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill – sequence: 13 givenname: Steven surname: Offenbacher fullname: Offenbacher, Steven organization: Center for Oral and Systemic Disease, School of Dentistry, University of North Carolina at Chapel Hill |
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Keywords | Periodontal Disease(s)/Periodontitis genomics genetics gingivitis bacteria plaque/plaque biofilms |
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