HHEX基因多态性与中国北方汉族人群精神分裂症及合并2型糖尿病发病的遗传学研究

Study of the HHEX gene polymorphism in schizophrenia patients with type-2 diabetes in a Chinese Han population

目的探讨2型糖尿病易感基因HHEX与中国汉族人群2型糖尿病、精神分裂症以及精神分裂症合并2型糖尿病发病的关系。方法采用群体遗传学研究策略,以中国北方汉族人群331例精神分裂症患者、166例精神分裂症合并2型糖尿病患者、229例单纯2型糖尿病患者和389例健康对照个体为研究对象,采用TaqMan探针方法检测HHEX基因rs1111875位点基因型。结果拟合优度χ^2检验分析显示rs1111875基因型频数分布在上述4个群体中均符合Hardy-Weinberg平衡定律（P〉0.05）;Pearsonχ^2检验显示HHEX基因rs1111875位点等位基因、基因型频率在上述4组中差异显著（χ-2=14.770,df=3,P=0.002;χ^2=15.102,df=6,P=0.019）。遗传学关联分析发现,与健康对照组比较,单纯2型糖尿病组rs1111875位点等位基因频率差异显著（χ^2=3.905,P=0.048）,单纯精神分裂症组或精神分裂症合并2型糖尿病组,rs1111875位点等位基因、基因型频率均无显著差异（P〉0.05）,结论 HHEX基因rs1111875位点与中国北方汉族人群2型糖尿病发病相关联,而与精神分裂症以及精神分裂症合并2型糖尿病发病无关联。

Objective To investigate the association of the HHEX gene with type-2diabetes（T2D）,schizophrenia and T2 Ddeveloped in patients with schizophrenia.Methods A strategy of population-based genetic research was applied for the present study.TaqMan protocol was used to genotype rs1111875 present in the HHEX gene in 331 patients with schizophrenia,166 of whom developed T2 D,229patients with T2 Donly and 389 controls.Results The goodness-of-fitχ-2 test showed that the genotypic distribution of rs1111875 was in Hardy-Weinberg equilibrium in all 4study populations.Pearsonχ-2 test revealed a significant difference in allelic and genotypic frequencies among these 4study populations（χ-2=14.770,df=3,P=0.002 for allelic association;χ^2=15.102,df=6,P=0.019 for genotypic association）,in which the frequency of rs1111875-G minor allele was significantly higher in the T2 Dgroup than the control group（χ^2=3.905,P=0.048）,although there was no difference in allelic and genotypic frequencies between any other groups.Conclusion The HHEX gene is associated only with T2 Dbut neither with schizophrenia nor with T2 D that was developed in patients with schizophrenia in the Chinese Han population from northern China.