Sunmin Park1, Meiling Liu1, Suna Kang1. 1. Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, South Korea.
Abstract
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.
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, CDKAL1rs7754840 and rs9460546, HHEXrs5015480, and OAS3rs2072134. 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.
Authors: Valérie de Crécy-Lagard; Pietro Boccaletto; Carl G Mangleburg; Puneet Sharma; Todd M Lowe; Sebastian A Leidel; Janusz M Bujnicki Journal: Nucleic Acids Res Date: 2019-03-18 Impact factor: 16.971