title: No Interaction with Alcohol Consumption, but Independent Effect of C12orf51 (HECTD4) on Type 2 Diabetes Mellitus in Korean Adults Aged 40-69 Years: The KoGES_Ansan and Ansung Study.
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.
authors.affiliation: Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, South Korea.|Institute for Health and Society, Hanyang University, Seoul, South Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, South Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lim
authors.affiliation: Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, South Korea.|Institute for Health and Society, Hanyang University, Seoul, South Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000209:etiology*; D004032:Diet; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D016016:Proportional Hazards Models; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C000609470:HECTD4 protein, human; D044767:Ubiquitin-Protein Ligases