245-LB: Association between the Risk of T2D Incidence and the Genetic Variants of GCK and HDAC4 Genes Interacting with Alcohol Consumption in Korea

Chronic alcohol consumption is well-known as an independent risk factor for type 2 diabetes (T2D), which is related with impaired glucose homeostasis and insulin resistance. The identification of genetic variants and the association with diseases may help to explain the genetic etiology of type 2 diabetes. In this study, we aimed to search for the single nucleotide polymorphisms (SNPs) associated with T2D risk, which also interact with alcohol consumption. We conducted genome-wide interaction study using the Korea Association Resource (KARE) data. We found that two SNPs, HDAC4 (rs3791370) and GCK (rs758989) are associated with T2D and also interact with alcohol consumption (odds ratio [OR] 1.74, and OR 1.37, respectively). We further investigated the association between these SNPs and response to alcohol consumption in risk of T2D incidence. In alcohol consumption group, these SNPs significantly increased the risk of T2D incidence compared with nonalcohol consumption group (HDAC4; hazard ratio [HR] 1.29, GCK; HR 1.34). Moreover, genotype association analysis showed that the presence of the risky allele (hetero risky allele [CR] + minor homo risky allele [RR]) in GCK SNP significantly increased the risk of T2D incidence (1.47, p = 0.032) compared with major homo C allele [CC] in alcohol consumption group after adjustment with age, BMI, smoking, physical activity, and history of diabetes. However, presence of the risky allele in HDAC4 SNP marginally increased the risk of T2D incidence (1.47, p = 0.0652). Based on our data, we suggest that HDAC4 and GCK SNPs could be a potential factor for increase of T2D incidence risk, which may be helpful to better understand the genetic basis of T2D in association with alcohol consumption.