Open AccessThe Novel ASIC2 Locus Is Associated with Severe Gingival Inflammation
Author(s) -
Shaoping Zhang,
Kimon Divaris,
Kevin Moss,
Na Yu,
Silvana P. Barros,
Julie T. Marchesan,
Thiago Morelli,
Cary S. Agler,
Steven J. Kim,
Di Wu,
Kari E. North,
James D. Beck,
Steven Offenbacher
Publication year - 2016
Publication title -
jdr clinical and translational research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.86
H-Index - 12
eISSN - 2380-0852
pISSN - 2380-0844
DOI - 10.1177/2380084416645290
Subject(s) - minor allele frequency , genome wide association study , odds ratio , allele , international hapmap project , locus (genetics) , single nucleotide polymorphism , genotyping , medicine , genetics , biology , genotype , gene
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 th 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.