摘要：目的  探讨糖皮质激素受体（GR）单核苷酸多态性与2型糖尿病（T2MD） 易感性及人体体型的相关性。方法  采用病例-对照研究设计，从解放军总医院健康体检中心的体检患者中，募集40例T2MD患者和127例对照。结合三种不同的SNP位点选择方法，采用上海天昊生物科技有限公司的iMLDRTM 多重SNP分型技术对入选SNP位点进行基因分型。采用非条件Logistic 回归，校正年龄、性别、吸烟、饮酒后，分析基因型与T2MD易感性的关系。得到的阳性位点，进一步采用协方差分析，校正年龄、性别、吸烟、饮酒后，评价其与体重指数（BMI）和腰臀比（WHR）的相关性。 结果  共选取14个SNP位点，其中rs10052957突变型在病例组中频率为零，故未纳入统计分析。所有的13个SNP位点在病例和对照组中的基因分型均符合Hardy-Weinberg平衡。rs9324924 TT基因型（OR [95%CI]= 3.12[1.06~9.17], P=0.039）和rs9324921 AA基因型（OR [95%CI]= 14.92[1.39~160.60], P=0.026）发生T2DM的风险较野生型增高，且两基因型的BMI[（P=0.023(rs9324924); P=0.002 (rs9324921)）]、WHR [P=0.033(rs9324924); P=0.003(rs9324921)] 也较野生型明显增高。结论  在本研究中，GR基因rs9324924、rs9324921与T2DM易感性和体型有关，其中纯和突变型T2DM发病风险明显增加，且更具有肥胖倾向。

Abstract：Objective To investigate the association of glucocorticoid receptor (GR) polymorphism with the susceptibility to type 2 diabetes mellitus (T2MD) and with the human somatotype in Chinese Han population. Methods We conducted a case-control genetic association study between 40 patients with T2MD and 127 controls, which were sequentially collected form physical examination center of Chinese PLA general hospital according to inclusion and exclusion criteria. Three different methods were used to determine the SNPs within GR gene (NR3C1). All the SNPs were genotyped using iMLDRTM genotyping technology. Unconditioned logistic regression analysis was used to explore the association of susceptibility to T2MD, while adjusting for age, sex, smoking and drinking status. The association of GR polymorphism with means of body mass index (BMI) and waist-to-hip ratio (WHR) were analyzed by ANCOVA using the general linear model procedure. Results Fourteen SNPs were genotyped in our study and rs10052957 was excluded because of rare mutation in case group. Genotype frequencies of the rest 13 SNPs were conformed to Hardy-weinberg equilibrium in both patients and control group. On the basis of unconditioned logistic regression analysis, rs9324924 TT and rs9324921 AA genotype were independently with the risk of T2MD, with OR (odd radio) of 3.12 [95% CI (confidence interval): 1.06-9.17, P=0.039] and OR of 14.92[1.39-160.60, P=0.026）respectively. ANCOVA analysis showed relation of rs9324924 TT and rs9324921 AA genotype with higher means of BMI (P=0.023 for rs9324924; P=0.002 for rs9324921) and WHR (P=0.033 for rs9324924; P=0.003 for rs9324921). Conclusion In our study, the rs9324924 and rs9324921 polymorphisms of GR gene are associated with the incidence of T2MD and human somatotype. Patients with rs9324924 TT and rs9324921 AA genotype are more susceptible to T2MD and more prone to be obesity.