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Interaction between the NOS3 gene and obesity as a determinant of risk of type 2 diabetes: the Atherosclerosis Risk in Communities study.

TitleInteraction between the NOS3 gene and obesity as a determinant of risk of type 2 diabetes: the Atherosclerosis Risk in Communities study.
Publication TypeJournal Article
Year of Publication2013
AuthorsBressler J, Pankow JS, Coresh JJ
Secondary AuthorsBoerwinkle E
JournalPLoS One
Volume8
Issue11
Paginatione79466
Date Published2013
ISSN1932-6203
KeywordsAged, Diabetes Mellitus, Type 2, Female, Genotype, Humans, Logistic Models, Male, Middle Aged, Nitric Oxide Synthase Type III, Obesity, Prospective Studies, Risk Factors
Abstract

Endothelial nitric oxide synthase 3 (NOS3) catalyzes the production of nitric oxide from L-arginine in endothelial cells. Obesity is a modifiable risk factor for diabetes, and obese individuals have been reported to have reduced nitric oxide availability compared to controls whose weight is in the normal range. Since homozygous carriers of the NOS3 G894T variant are predicted to have decreased enzyme activity, the association between NOS3 genotype and type 2 diabetes, and possible effect modification by body mass index (BMI) were evaluated. The prevalence of diabetes and BMI was determined at baseline in 14,374 participants 45-66 years of age from the prospective biracial population-based Atherosclerosis Risk in Communities (ARIC) Study of the development of atherosclerosis in four communities in the United States. Individuals with a BMI ≥30 kg/m(2) were considered obese. Those subjects not meeting the case definition were the comparison groups for the 728 African American and 980 white participants with diabetes. Multivariable logistic regression models adjusted for age, sex, and field center were used to test for main genetic effects and interaction with obesity. Although the NOS3 G894T variant was not independently associated with diabetes in either African Americans or whites, significant interaction between BMI and the NOS3 polymorphism indicated that obesity was an effect modifier of diabetes risk for white individuals with the TT genotype (odds ratio (OR) for interaction = 1.65, p = 0.04). In stratified analyses, homozygosity for the NOS3 T allele in obese white participants but not in those whose BMI

DOI10.1371/journal.pone.0079466
Alternate JournalPLoS One
PubMed ID24278136
PubMed Central IDPMC3835793
Grant ListHHSN2682011000010C / / PHS HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN2682011000012C / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States
HHSN2682011000011C / / PHS HHS / United States