title: Variant of the clock circadian regulator (CLOCK) gene and related haplotypes are associated with the prevalence of type 2 diabetes in the Japanese population.
abstract: 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/m(2) ), overweight (BMI ≥23 kg/m(2) ), 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.
authors.affiliation: Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Uemura
authors.affiliation: Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Sakurako
authors.initials: S
authors.lastname: Katsuura-Kamano
authors.affiliation: Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors.forename: Kokichi
authors.initials: K
authors.lastname: Arisawa
authors.affiliation: Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Sayo
authors.initials: S
authors.lastname: Kawai
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.affiliation: Department of Community and International Health Nursing, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Shinchi
authors.affiliation: Department of Public Health, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takashima
authors.affiliation: Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakahata
authors.affiliation: Division of Epidemiology, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Mikami
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.affiliation: Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Nagato
authors.initials: N
authors.lastname: Kuriyama
authors.affiliation: Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D056926:CLOCK Proteins / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011795:Surveys and Questionnaires
chemical_list: D056926:CLOCK Proteins; C538943:CLOCK protein, human
keywords: 2型糖尿病; cross-sectional studies; single nucleotide polymorphism; type 2 diabetes mellitus; 单核苷酸多态性; 横断面研究