精神分裂症伴发2型糖尿病与烟碱型乙酰胆碱受体基因多态性关联研究

The study on the association between neuronal nicotinic acetylcholine receptor subunit genes and type 2 diabetes in Chinese Han schizophrenics

目的在中国汉族精神分裂症患者中探讨烟碱型乙酰胆碱受体基因多态性与2型糖尿病共病的关联。方法采用Taq Man荧光探针基因分型技术对346例伴发2型糖尿病的中国汉族精神分裂症患者和360例不伴糖尿病的精神分裂症患者的α3、α4、α7、α5烟碱型乙酰胆碱受体(neuronal nicotinic acetylcholine receptor,n Ach R)基因即CHRNA3(rs1317286)、CHRNA4(rs1044396)、CHRNA7(rs6494212)及CHRNA5(rs16969968、rs684513)多态位点进行基因分型,比较等位基因频率和基因型频率,并进一步进行基因-基因交互作用分析。结果单位点分析显示男性患者rs6494212位点的等位基因分布和基因型分布在两组间差异均有统计学意义(P<0.05);rs1317286、rs1044396、rs16969968、rs684513位点的基因型分布和等位基因分布均无明显差异(P均>0.05)。CHRNA5基因的两个单核苷酸多态位点(single nucleotide polymorphisms,SNPs)组成的单体型与两组疾病共病关联无统计学意义(P>0.05)。进一步基因交互作用分析显示rs131726、rs1044396、rs6494212及rs684513这4个位点的联合作用模式可能与两组疾病共病相关(P=0.002)。结论 CHRNA7(rs6494212)可能是中国汉族男性精神分裂症患者患2型糖尿病的易感基因。rs1317286、rs1044396、rs6494212及rs684513位点的联合作用可能与精神分裂症共病2型糖尿病相关。

Objective To explore the relationships between neuronal nicotinic acetylcholine receptor subunit gene polymorphisms and type 2 diabetes in Chinese han schizophrenics. Methods Five single nucleotide polymorphisms（SNPs）of CHRNA3（rs1317286）,CHRNA4（rs1044396）,CHRNA7（rs6494212） and CHRNA5（rs16969968,rs684513） gene were analyzed in a sample of 346 schizophrenics with type 2 diabetes and 360 schizophrenics without type 2 diabetes. The five markers were genotyped by the Taq Man fluorogenic detection method with the ABI7900. Results There were no significant differences in alleles and genotypes distribution of the five genes between two groups（P〉0.05）. For the CHRNA7（rs6494212）, there were significant difference in genotypes（P=0.039） and alleles distribution（P〈0.021） between two groups in male patients.The haplotypes constructed by markers of CHRNA5 were not associated with the 2diabetes in Chinese Han male schizophrenics.The interaction analysis revealed a significant association between models made up by rs1317286,rs1044396,rs6494212,rs684513 and 2 diabetes in Chinese Han male schizophrenics（P=0.002）.Conclusion The CHRNA7（rs6494212）gene may be one of common susceptible genes for 2 diabetes in ChineseHanmaleschizophrenics.Thereisasignificantassociationbetweenmodelsmadeupby rs131726rs1044396,rs6494212,rs684513 and schizophrenics with type 2 diabetes.