Hirokazu Uemura1, Sakurako Katsuura-Kamano1, Miwa Yamaguchi1, Kokichi Arisawa1, Nobuyuki Hamajima2, Asahi Hishida3, Sayo Kawai3, Isao Oze4, Koichi Shinchi5, Naoyuki Takashima6, Sadao Suzuki7, Noriko Nakahata8, Haruo Mikami9, Keizo Ohnaka10, Nagato Kuriyama11, Michiaki Kubo12, Hideo Tanaka4. 1. Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. 2. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan. 3. Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. 4. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. 5. Department of Community and International Health Nursing, Faculty of Medicine, Saga University, Saga, Japan. 6. Department of Public Health, Shiga University of Medical Science, Otsu, Japan. 7. Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 8. Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. 9. Division of Epidemiology, Chiba Cancer Center Research Institute, Chiba, Japan. 10. Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 11. Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. 12. Laboratory for Genotyping Development, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
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.
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: Dolores Corella; Eva M Asensio; Oscar Coltell; José V Sorlí; Ramón Estruch; Miguel Ángel Martínez-González; Jordi Salas-Salvadó; Olga Castañer; Fernando Arós; José Lapetra; Lluís Serra-Majem; Enrique Gómez-Gracia; Carolina Ortega-Azorín; Miquel Fiol; Javier Díez Espino; Andrés Díaz-López; Montserrat Fitó; Emilio Ros; José M Ordovás Journal: Cardiovasc Diabetol Date: 2016-01-07 Impact factor: 9.951