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The Novel Locus is Associated with Severe Gingival Inflammation.

TitleThe Novel Locus is Associated with Severe Gingival Inflammation.
Publication TypeJournal Article
Year of Publication2016
AuthorsZhang S, Divaris K, Moss K, Yu N, Barros S, Marchesan J, Morelli T, Agler C, Kim SJ, Wu D, North KE, Beck J
Secondary AuthorsOffenbacher S
JournalJDR Clin Trans Res
Volume1
Issue2
Pagination163-170
Date Published2016 Jul
ISSN2380-0844
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.

DOI10.1177/2380084416645290
Alternate JournalJDR Clin Trans Res
PubMed ID28459102
PubMed Central IDPMC5409514
Grant ListHHSN268201100009I / HL / NHLBI NIH HHS / United States
K23 DE025093 / DE / NIDCR NIH HHS / United States
R01 DE011551 / DE / NIDCR NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
T90 DE021986 / DE / NIDCR NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
R01 DE023836 / DE / NIDCR NIH HHS / United States
R90 DE022527 / DE / NIDCR NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 DE021418 / DE / NIDCR NIH HHS / United States