Association of disease‐predisposition polymorphisms of the melatonin receptors and sunshine duration in the global human populations |
| |
| Authors: | Lin‐dan Ji Jin Xu Dong‐dong Wu Si‐da Xie Nelson L S Tang Ya‐ping Zhang |
| |
| Institution: | 1. Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou, China;2. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China;3. KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming, China;4. Institute of Public Health, School of Medicine, Ningbo University, Ningbo, China;5. Graduate School of the Chinese Academy of Sciences, Beijing, China;6. Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China;7. Laboratory for Genetics of Disease Susceptibility, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China;8. Laboratory for Conservation and Utilization of Bio‐resource, Yunnan University, Kunming, China |
| |
| Abstract: | Abstract: Melatonin is predominantly involved in signaling circadian and seasonal rhythms, and its synthesis is regulated by the environmental light/dark cycle. The selection pressure by geographically different environmental light/dark cycles, which is predominantly determined by sunshine duration, on the global distribution of genetic polymorphisms in the melatonin pathway is not well understood. Recent genetic association studies identified various disease‐predisposition polymorphisms in this pathway. We investigated the correlations between the prevalence of these clinically important single nucleotide polymorphisms (SNPs) and sunshine duration among worldwide human populations from twelve regions in the CEPH‐HGDP database rs4753426, a recently reported predisposition SNP for type 2 diabetes in the promoter of the MT2 melatonin receptor gene (MTNR1B), which was not included in the CEPH‐HGDP genotyping array, was additionally genotyped. This SNP showed a marginally significant correlation in 760 CEPH‐HGDP DNA samples (r = ?0.5346, P = 0.0733), and it showed the most prominent association among the candidate melatonin pathway SNPs examined. To control for population structure, which may lead to a false positive correlation, we genotyped this SNP in a replication set of 1792 subjects from China. The correlation was confirmed among Chinese populations (r = ?0.8694, P = 0.0002), and was also statistically significant after correction of other climatic and geographical covariants in multiple regression analysis (β = ?0.907, P = 1.94 × 10?5). Taken together, it suggests that the human melatonin signaling pathway, particularly MT2 melatonin receptor may have undergone a selective pressure in response to global variation in sunshine duration. |
| |
| Keywords: | association study melatonin pathway melatonin receptor 1B natural selection sunshine duration |
|
|
