FTO基因变异与生活方式的交互作用对代谢综合征的影响

Effect of interactions between FTO gene variation and lifestyle on metabolic syndrome

目的探讨脂肪量和肥胖相关因子(FTO)基因rs9939609单核苷酸多态性(SNP)与生活方式的交互作用对代谢综合征(MS)的影响。方法在重庆地区人群中随机选择MS患者269例和正常对照(NC)263例,应用TaqMan探针等位基因特异性杂交分析法检测FTO基因rs9939609单核苷酸多态性,计算基因频率分布并比较不同基因型亚组间的各种临床代谢参数。用logistic回归分析FTO基因多态性与生活方式的交互作用对MS的影响。结果FTO基因rs9939609多态性位点共检测出TT、AT、AA3种基因型,频率分别为76.32%、21.99%和1.69%,符合Hardy-Weinberg平衡。MS组A等位基因的频率(15.43%)显著高于NC组(9.89%),A等位基因携带者患MS的风险为T等位基因携带者的1.863倍(OR=1.863,95%CI1.231～2.819,χ2=8.674,P=0.003),FTO基因变异通过体重指数(BMI)与MS相关,生活方式与FTO基因的交互作用与MS未发现相关性。结论FTO基因rs9939609多态性位点的A等位基因可能是MS的风险等位基因,它通过BMI起作用,生活方式与FTO基因的交互作用与MS的相关性有待进一步研究。

Objective To study the effect of interactions between the single nucleotide polymorphism （SNP） of rs9939609 in fat mass and obesity associated gene （FTO） and lifestyle on metabolic syndrome （MS）. Methods Two hundred and sixty nine patients with MS （MS group） and 263 controls （control group） were randomly enrolled from Chongqing area. Genotyping of FTO rs9939609 polymorphism was performed using an allelic discrimination assay with TaqMan probes. The distribution of allele frequency was computed and the various clinical metabolic parameters of different genotype subgroups were compared. Examination of gene-lifestyle interactions with MS was analyzed by logistic regression. Results Genotype frequencies of TT, AT and AA were 76.32%, 21.99% and 1.69%, respectively. There was no significant deviation from Hardy-Weinberg equilibrium. The frequency of carriers of the A allele was significantly higher in MS group than in control group. The A allele of rs9939609 significantly increased the risk of MS with odd ratio （OR） of 1.863 [OR=1.863, 95%CI （1.231~2.819）, χ2=8.674, P=0.003]. A common variant in the FTO gene was associated with MS through an effect on body mass index （BMI）. No interaction was found between the FTO rs9939609 genotype and lifestyle. Conclusions It is indicated that an allele polymorphism of rs9939609 site in FTO gene may be a risk factor for MS through an effect on body mass index （BMI）. Examination of gene-lifestyle interactions may provide further insights into the role of FTO in the pathogenesis of human obesity and MS.