Alcohol Intake Interacts with CDKAL1, HHEX, and OAS3 Genetic Variants, Associated with the Risk of Type 2 Diabetes by Lowering Insulin Secretion in Korean Adults.

BACKGROUND:Since alcohol intake increases the prevalence of type 2 diabetes (T2DM) in Koreans, we tested the hypothesis that the interactions of genetic variants involved in β-cell function and mass with alcohol intake increase the T2DM risk. METHODS:The single nucleotide polymorphisms (SNPs) were selected by genome-wide association study for insulin secretion after adjusting for age, gender, area of residence, body mass index, and alcohol intake (p < 1 × 10^-4 ) in 8,842 middle-aged adults in the Ansan/Ansung cohort. Genetic risk scores (GRSs) were calculated by summing the risk alleles of 4 selected SNPs, CDKAL1 rs7754840 and rs9460546, HHEX rs5015480, and OAS3 rs2072134. The GRSs were categorized into 3 groups by tertiles, and the association between GRS and insulin secretion was measured using logistic regression after adjusting for confounding factors in the Ansan/Ansung cohort. The results were confirmed by the Rural cohort. RESULTS:HOMA-IR was higher and HOMA-B was much lower in the High-GRS than the Low-GRS in both cohorts. T2DM risk was higher by approximately 1.5-fold in the High-GRS than in the Low-GRS in both cohorts. In the High-GRS group, HOMA-B decreased by 0.89- and 0.62-fold in comparison with the Low-GRS in the Ansan/Ansung cohort and Rural cohort. The GRS interacted with alcohol intake to increase the risk of developing T2DM in the Ansan/Ansung cohort (p = 0.036) and Rural cohort (p = 0.071). The risk of T2DM increased in the High-GRS group with high alcohol intake and it was associated with decreased HOMA-B. High alcohol intake decreased HOMA-B regardless of GRS, and HOMA-B was lower in the descending order of Medium-GRS, Low-GRS, and High-GRS. However, HOMA-IR was not altered by alcohol intake, but was elevated in the High-GRS more than in the other groups. CONCLUSIONS:Subjects with a High-GRS had an elevated risk of T2DM even with moderate alcohol intakes due to lower HOMA-B. High alcohol intake appears to be a risk factor for all Asians regardless of alcohol intake. © 2018 by the Research Society on Alcoholism.

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