Variant of the clock circadian regulator (CLOCK) gene and related haplotypes are associated with the prevalence of type 2 diabetes in the Japanese population

Background: Circadian rhythm disruptions can cause various health disorders. The present study evaluated associations between single nucleotide polymorphisms in the core circadian gene clock circadian regulator (CLOCK) and the prevalence of type 2 diabetes (T2D) in the Japanese population. Methods: Cross-sectional data were analyzed from 2485 subjects (1243 men, 1242 women; age 35–69 years) enrolled in the baseline surveys of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Associations between three CLOCK gene polymorphisms (rs1801260, rs3736544, and rs4864548) and the prevalence of obesity (body mass index [BMI] ≥25 kg/m²), overweight (BMI ≥23 kg/m²), and T2D were evaluated by logistic regression analyses; haplotype analysis and stratified analyses for the prevalence of diabetes were also conducted. Results: Compared with those who were homozygous for the respective major alleles, subjects with the rs1801260 minor allele C had a significantly higher odds ratio (1.5; 95% confidence interval 1.1–2.1) for the prevalence of diabetes after adjustment for potential confounding factors, including BMI. When stratified by overweight, the associations between rs1801260 and the prevalence of diabetes were marked and significant in non-overweight subjects, but not in overweight subjects. The TGA (rs1801260–rs3736544–rs4864548) haplotype was associated with a lower prevalence of diabetes, whereas the CGG haplotype was associated with a higher prevalence of diabetes. Conclusions: Variant of the CLOCK gene and related haplotypes are associated with the prevalence of T2D in the Japanese population, in which obesity is less common, and the association between CLOCK gene variant at rs1801260 and the prevalence of diabetes is enhanced in normal-weight subjects.