Search resultsAlcohol intake interacts with CDKAL1, HHEX and OAS3 genetic variants, associated with insulin secretion, to increase the risk of type 2 diabetes 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 SNPs were selected by GWAS for insulin secretion after adjusting for age, gender, area of residence, BMI and alcohol intake(P<1X10 ) in 8842 middle-aged adults in the Ansan/Ansung cohorts. Genetic risk scores(GRSs) were calculated by summing the risk alleles of selected 4 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 folds in the High-GRS than in the Low-GRS in both cohorts. In the High-GRS group, HOMA-B decreased by 0.85 and 0.62 folds in comparison to 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 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. This article is protected by copyright. All rights reserved.