褪黑激素通路是生物節(jié)律信號轉(zhuǎn)導(dǎo)的主要途徑之一,，受環(huán)境日/夜周期影響。世界范圍內(nèi)不同的日照時長及相應(yīng)的晝夜節(jié)律的自然選擇作用很可能對褪黑激素通路的遺傳多態(tài)起著重要的作用,。
在中國科學(xué)院昆明動物研究所張亞平院士及香港中文大學(xué)鄧亮生教授的共同指導(dǎo)下,，博士研究生季林丹等研究人員對世界人群（CEPH-HGDP）褪黑激素通路基因多態(tài)性與日照時長的相關(guān)性進(jìn)行了系統(tǒng)分析。研究提示,，在全世界范圍內(nèi)人群中褪黑激素受體MT2（MTNR1B）基因的多態(tài)性與日照密切相關(guān),，該研究結(jié)果同時在中國群體中得到驗證。因此,，褪黑激素通路,，尤其MT2受體的遺傳多態(tài)性很可能經(jīng)歷了日照的自然選擇。
此外,，該遺傳多態(tài)性在前期與香港中文大學(xué)的合作研究中發(fā)現(xiàn)與青少年特發(fā)性脊柱側(cè)凸（Adolescent Idiopathic scoliosis, AIS）發(fā)病相關(guān),；近期報道的全基因組研究（GWAS）也提示其為二型糖尿病(Type 2 Diabetes Mellitus, T2D)的易感位點。
綜合研究結(jié)果提示,，日照時長的自然選擇作用可能促使形成了MTNR1B基因遺傳位點的多態(tài),；但隨著自然環(huán)境及生活方式的改變，該多態(tài)性反而可能成為疾病易感因素。該研究是闡釋復(fù)雜疾病易感位點經(jīng)歷環(huán)境自然選擇假說的一次成功示例,，更重要是也可為二型糖尿病及青少年特發(fā)性脊柱側(cè)凸等疾病臨床診治等提供新的信息,。
該研究結(jié)果近期發(fā)表在Journal of Pineal Research上。(生物谷Bioon.com)
生物谷推薦原文出處：
Journal of Pineal Research doi:10.1111/j.1600-079X.2009.00736.x
Association of disease-predisposition polymorphisms of the melatonin receptors and sunshine duration in the global human populations
Lin-dan Ji 1,2,3*, Jin Xu 4*, Dong-dong Wu 2,5 , Si-da Xie 3,6 , Nelson L. S. Tang 3,6,7 and Ya-ping Zhang 2,3,8
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: 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.
