近日，糖尿病领域权威杂志《糖尿病》（Diabetes）发表了中科院上海生命科学研究院营养科学研究所林旭博士研究组在糖尿病人群遗传学研究中的一项最新发现。
肥胖是导致II型糖尿病、心脑血管疾病和高血压的主要危险因素，而了解肥胖的遗传学基础是预防和控制肥胖发生的关键。最近，英国Peninsula医学院的Frayling等人通过全基因组关联研究发现位于脂肪和肥胖相关基因（fat mass an obesity associated gene, FTO）上的SNP（单核苷酸多态性，用于揭示遗传学改变）与肥胖和II型糖尿病的发病风险有很强的关联关系。随后另外两个研究组也发现位于FTO基因上的SNP位点与成年人肥胖和儿童肥胖均有很强的相关关系。但是这些研究结果都是在欧洲白人人群中取得的，而在中国汉族人群中FTO基因上的这些SNP位点是否与肥胖和II型糖尿病的发病风险也存在着相似的关联关系尚不清楚。
林旭研究组的黎怀星博士和博士生邬莹等人以参加“中国老龄人口营养健康状况”项目的北京和上海市汉族居民为基础，系统研究了FTO基因上多个SNP位点与肥胖和II型糖尿病的关联关系。他们发现：（1）在中国汉族人群内FTO基因上的SNP位点与肥胖、超重以及肥胖相关的数量性状（体质指数、体脂含量和腰围）之间均没有任何的关联关系；（2）FTO基因上的SNP位点与II型糖尿病、空腹血糖损伤以及糖尿病相关的数量性状（空腹血糖、糖化血红蛋白、胰岛素和胰岛素分泌指数）之间也没有显著的相关关系；（3）FTO基因的遗传结构和等位基因频率在中国汉族人群和欧洲白种人群之间存在着显著的差异。根据这些研究结果，作者认为在中国汉族人群内FTO基因上的遗传多态性位点不是增加肥胖和II型糖尿病发病风险的主要危险因素，这些SNP在中国汉族人群和欧洲白种人群之间的功能差异可能是由于其等位基因频率和基因结构的差异所导致的。
本研究首次在中国汉族人群内研究FTO基因上的SNP位点与肥胖和II型糖尿病的关联关系，其结果不仅为在不同种族之间进行基因功能的比较分析创造了条件，而且也为正确分析和判断影响肥胖和糖尿病发病风险的遗传变异提供了有价值的资料。
该项工作得到了国家自然科学基金、中科院知识创新工程重大项目课题、中科院创新经费、上海市科委以及联合利华发展基金的资助。（上海生命科学研究院）
原始出处:
Diabetes Publish Ahead of Print published online ahead of print October 24, 2007
DOI: 10.2337/db07-1130
Variants in FTO gene are not associated with obesity in a Chinese Han population
Huaixing Li1, Ying Wu1, Ruth J.F. Loos2, Frank B. Hu3, Yong Liu1, Jing Wang1, Zhijie Yu1, and Xu Lin1
1Key Laboratory of Systems Biology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China
2MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Box 285, Hills Road, Cambridge, CB2 0QQ, UK
3Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
Objective.: Recently, genome-wide association studies have provided evidence that several common variants within fat mass and obesity associated gene (FTO) gene were significantly associated with obesity in populations of European origin. However, their effects in other ethnic populations remain to be elucidated.
Research Design and Methods.: In this study, we examined the association between three FTO variants (rs8050136, rs9939609 and rs9930506) and obesity and related traits in a population-based study of 3,210 unrelated Chinese Hans from Shanghai and Beijing. In secondary analyses, we also tested for association with type 2 diabetes and related traits. Logistics regression and generalized linear models were used to test for additive and dominant effects of the risk alleles.
Results.: The minor allele frequencies (MAF) in our population (0.12, 0.11, and 0.20, respectively) were substantially lower than those observed for populations of European descent (e.g. for CEU population of HapMap: 0.45, 0.48, and 0.45, respectively). Despite our study being sufficiently powered to detect effects similar to those previously reported, none of the FTO SNPs were found to be associated with obesity, overweight, BMI, waist circumference and body fat percentage. In addition, none of the SNPs exhibited significant associations with fasting levels of plasma glucose, HbA1c, insulin and ß-cell function (estimated as HOMA-B) under either additive or dominant model in the quantitative trait analyses. Analyses stratified by sex or geographical region did not change these observations.
Conclusion.: Therefore, our data do not support that the FTO common variants are major contributors of obesity or type 2 diabetes in the Chinese Han population.
