Abstract
Previously, genetic polymorphisms of C12orf51 (HECTD4) (rs2074356 and/or rs11066280) have been shown to be related to alcohol consumption and type 2 diabetes (T2D). This study aimed to prospectively examine whether C12orf51 had an interaction with or independent effect on alcohol consumption and the risk of T2D. The present study included 3,244 men and 3,629 women aged 40 to 69 years who participated in the Korean Genome and Epidemiology Study (KoGES)_Ansan and Ansung Study. Cox proportional hazards models were used to estimate HRs and 95% CIs for T2D. rs2074356 and rs11066280 were associated with the risk of T2D after adjusting for alcohol consumption (rs2074356 for AA: HR = 0.39 and 95% CI = 0.17–0.87 in men, and HR = 0.36 and 95% CI = 0.13–0.96 in women; rs11066280 for AA: HR = 0.44 and 95% CI = 0.23–0.86 in men, and HR = 0.39 and 95% CI = 0.16–0.94 in women). We identified that the association of each variant (rs2074356 and rs11065756) in C12orf51 was nearly unchanged after adjusted for alcohol consumption. Therefore, the association of 2 SNPs in C12orf51 with diabetes may not be mediated by alcohol use. There was no interaction effect between alcohol consumption and the SNPs with T2D. However, even in never-drinkers, minor allele homozygote strongly influenced T2D risk reduction (rs2074356 for AA: HR = 0.35, 95% CI = 0.14–0.90, and p-trend = 0.0035 in men and HR = 0.34, 95% CI = 0.13–0.93, and p-trend = 0.2348 in women; rs11066280 for AA: HR = 0.36, 95% CI = 0.16–0.82, and p-trend = 0.0014 in men and HR = 0.39, 95% CI = 0.16–0.95, and p-trend = 0.3790 in women), while alcohol consumption did not influence the risk of T2D within each genotype. rs2074356 and rs11066280 in or near C12orf51, which is related to alcohol drinking behavior, may longitudinally decrease the risk of T2D, but not through regulation of alcohol consumption.
Highlights
Diabetes is a major global health problem
We evaluated the prospective association between rs2074356 and rs11066280 in the C12orf51 gene and the risk of type 2 diabetes (T2D) and examined whether there was the interaction of these two single nucleotide polymorphisms (SNPs) with alcohol consumption or whether there was the association between SNPs and the risk of T2D unrelated to alcohol use by alcohol consumption-specific subgroup analysis among adults aged 40–69 years in a prospective cohort study, the Korean Genome and Epidemiology Study (KoGES)_Ansan and Ansung Study
Hazard ratios (HRs) and 95% CIs of T2D according to genotypes of two SNPs in C12orf51 are shown in Fig 1. rs2074356 and rs11066280 were associated with the risk of T2D after adjusting for alcohol consumption in both men and women
Summary
Diabetes is a major global health problem. It is estimated that 382 million people or 8.3% of adults worldwide had diabetes in 2013 [1]. In Korea, the prevalence of diabetes has increased from 1.5% in 1971 to 11.9% in 2013 [2, 3]. Moderate alcohol consumption is generally associated with reduced risk of diabetes [6]. This protective association is thought to be due to improved insulin sensitivity [7]. Beneficial effects of alcohol consumption have not been consistent across studies. This discrepancy may be explained by different confounding structure between Asian and Western countries and, could be explained by genetic mechanisms that regulate alcohol intake and metabolism [8]
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