Racial/Ethnic Differences in Association of Fasting Glucose–Associated Genomic Loci With Fasting Glucose, HOMA-B, and Impaired Fasting Glucose in the U.S. Adult Population

Abstract

OBJECTIVE To estimate allele frequencies and the marginal and combined effects of novel fasting glucose (FG)-associated single nucleotide polymorphisms (SNPs) on FG levels and on risk of impaired FG (IFG) among non-Hispanic white, non-Hispanic black, and Mexican Americans. RESEARCH DESIGN AND METHODS DNA samples from 3,024 adult fasting participants in the National Health and Nutrition Examination Survey (NHANES) III (1991–1994) were genotyped for 16 novel FG-associated SNPs in multiple genes. We determined the allele frequencies and influence of these SNPs alone and in a weighted genetic risk score on FG, homeostasis model assessment of β-cell function (HOMA-B), and IFG by race/ethnicity, while adjusting for age and sex. RESULTS All allele frequencies varied significantly by race/ethnicity. A weighted genetic risk score, based on 16 SNPs, was associated with a 0.022 mmol/l (95% CI 0.009–0.035), 0.036 mmol/l (0.019–0.052), and 0.033 mmol/l (0.020–0.046) increase in FG levels per risk allele among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans, respectively. Adjusted odds ratios for IFG were 1.78 for non-Hispanic whites (95% CI 1.00–3.17), 2.40 for non-Hispanic blacks (1.07–5.37), and 2.39 for Mexican Americans (1.37–4.14) when we compared the highest with the lowest quintiles of genetic risk score (P = 0.365 for testing heterogeneity of effect across race/ethnicity). CONCLUSIONS We conclude that allele frequencies of 16 novel FG-associated SNPs vary significantly by race/ethnicity, but the influence of these SNPs on FG levels, HOMA-B, and IFG were generally consistent across all racial/ethnic groups.