近日,，糖尿病領(lǐng)域權(quán)威雜志《糖尿病》（Diabetes）發(fā)表了中科院上海生命科學(xué)研究院營養(yǎng)科學(xué)研究所林旭博士研究組在糖尿病人群遺傳學(xué)研究中的一項(xiàng)最新發(fā)現(xiàn),。
肥胖是導(dǎo)致II型糖尿病、心腦血管疾病和高血壓的主要危險(xiǎn)因素,，而了解肥胖的遺傳學(xué)基礎(chǔ)是預(yù)防和控制肥胖發(fā)生的關(guān)鍵,。最近,，英國Peninsula醫(yī)學(xué)院的Frayling等人通過全基因組關(guān)聯(lián)研究發(fā)現(xiàn)位于脂肪和肥胖相關(guān)基因（fat mass an obesity associated gene, FTO）上的SNP（單核苷酸多態(tài)性,，用于揭示遺傳學(xué)改變）與肥胖和II型糖尿病的發(fā)病風(fēng)險(xiǎn)有很強(qiáng)的關(guān)聯(lián)關(guān)系,。隨后另外兩個(gè)研究組也發(fā)現(xiàn)位于FTO基因上的SNP位點(diǎn)與成年人肥胖和兒童肥胖均有很強(qiáng)的相關(guān)關(guān)系,。但是這些研究結(jié)果都是在歐洲白人人群中取得的，而在中國漢族人群中FTO基因上的這些SNP位點(diǎn)是否與肥胖和II型糖尿病的發(fā)病風(fēng)險(xiǎn)也存在著相似的關(guān)聯(lián)關(guān)系尚不清楚,。
林旭研究組的黎懷星博士和博士生鄔瑩等人以參加“中國老齡人口營養(yǎng)健康狀況”項(xiàng)目的北京和上海市漢族居民為基礎(chǔ),，系統(tǒng)研究了FTO基因上多個(gè)SNP位點(diǎn)與肥胖和II型糖尿病的關(guān)聯(lián)關(guān)系。他們發(fā)現(xiàn)：（1）在中國漢族人群內(nèi)FTO基因上的SNP位點(diǎn)與肥胖,、超重以及肥胖相關(guān)的數(shù)量性狀（體質(zhì)指數(shù),、體脂含量和腰圍）之間均沒有任何的關(guān)聯(lián)關(guān)系；（2）FTO基因上的SNP位點(diǎn)與II型糖尿病,、空腹血糖損傷以及糖尿病相關(guān)的數(shù)量性狀（空腹血糖,、糖化血紅蛋白、胰島素和胰島素分泌指數(shù)）之間也沒有顯著的相關(guān)關(guān)系,；（3）FTO基因的遺傳結(jié)構(gòu)和等位基因頻率在中國漢族人群和歐洲白種人群之間存在著顯著的差異,。根據(jù)這些研究結(jié)果,，作者認(rèn)為在中國漢族人群內(nèi)FTO基因上的遺傳多態(tài)性位點(diǎn)不是增加肥胖和II型糖尿病發(fā)病風(fēng)險(xiǎn)的主要危險(xiǎn)因素,，這些SNP在中國漢族人群和歐洲白種人群之間的功能差異可能是由于其等位基因頻率和基因結(jié)構(gòu)的差異所導(dǎo)致的,。
本研究首次在中國漢族人群內(nèi)研究FTO基因上的SNP位點(diǎn)與肥胖和II型糖尿病的關(guān)聯(lián)關(guān)系，其結(jié)果不僅為在不同種族之間進(jìn)行基因功能的比較分析創(chuàng)造了條件,，而且也為正確分析和判斷影響肥胖和糖尿病發(fā)病風(fēng)險(xiǎn)的遺傳變異提供了有價(jià)值的資料。
該項(xiàng)工作得到了國家自然科學(xué)基金、中科院知識創(chuàng)新工程重大項(xiàng)目課題,、中科院創(chuàng)新經(jīng)費(fèi),、上海市科委以及聯(lián)合利華發(fā)展基金的資助,。（上海生命科學(xué)研究院）
原始出處:
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.
