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JDR Clin Trans Res. 2016 Jul;1(2):163-170. doi: 10.1177/2380084416645290. Epub 2016 Apr 20.

The Novel ASIC2 Locus is Associated with Severe Gingival Inflammation.

Author information

1
Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill.
2
Center for Oral and Systemic Disease, School of Dentistry, University of North Carolina at Chapel Hill.
3
Department of Pediatric Dentistry, School of Dentistry, University of North Carolina at Chapel Hill.
4
Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill.
5
Center for Oral & Craniofacial Health Sciences, School of Dentistry, University of North Carolina at Chapel Hill.
6
Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill Gillings School of Global Public Health.
7
Department of Dental Ecology, School of Dentistry, University of North Carolina at Chapel Hill.

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 90th 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 ASIC2 (acid sensing ionic channel-2, formerly named ACCN1); odds ratio=2.1, 95% confidence interval=1.6-2.7, p=3.9×10-8]. 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 ASIC2 is significantly associated with severe gingival inflammation and the association is plaque-independent.

KEYWORDS:

Periodontal Disease(s)/Periodontitis; bacteria; genetics; genomics; gingivitis; plaque/plaque biofilms

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