神经型烟碱乙酰胆碱受体α7亚单位基因多态性与精神分裂症的传递不平衡研究

The transmission disequih＇brium analysis between neuronal nicotinic acetylcholine receptor α7 subunit gene poly-morphisms and schizophrenia

目的探讨神经型烟碱乙酰胆碱受体订亚单位基因（neuronal nicotinic acetylcholine receptor α7 subunit gene，CHRNA7）多态性与精神分裂症的关系。方法应用聚合酶链反应及聚丙烯酰胺凝胶芯片技术检测129个精神分裂症先证者核心家系CHRNA7基因的rs2337980、rsl909884、rs883473三个单核苷酸多态性，并采用基于单倍型的单倍型相对风险检验（haplotype relative risk，HHRR）、传递不平衡检验（transmission disequilibrium test，TDT）及单倍型分析进行统计。结果（1）HHRR分析结果显示rs2337980位点精神分裂症患者组与虚拟对照组之间等位基因频率差异有统计学意义（P=0．017）；（2）TDT分析发现，rs2337980位点与精神分裂症之间可能存在传递不平衡，杂合子父母过多的传递等位基因C给患病子女（P=0．021）。（3）单倍型分析发现，rs2337980、rsl909884及rs2337980、rsl909884、rs883473组成的单倍型与精神分裂症有显著相关（总体P=0.034；global P=0．027），其中T-C，T-C-T两个单倍型与精神分裂症可能存在传递不平衡。结论CHRNA7基因多态性可能与精神分裂症存在关联，rs2337980的变异等位基因T可能是精神分裂症的保护性因子。

Objective To investigate the association between neuronal nicotinic acetylcholine receptor α7 subunit （CHRNA7） gene and schizophrenia. Methods The three polymorphisms rs2337980, rs1909884, rs883473 in CHRNA7 gene were detected based on PCR and polyacrylamide gel microarray in 129 schizophrenic trios. The results of genotyping were analyzed by haplotype relative risk analysis based on haplotype（ HHRR）, transmission disequilibrium test （TDT） and hyplotype analysis. Results （1） The HHRR analysis suggested that there was significant differences in rs2337980 allele frequencies between schizophrenia group and dummy control group（ P = 0.017） ; （2）In TDT test, there may be transmission disequilibrium between rs2337980 and schizophrenia, the heterozygous parents excessively transferred the C allele to patients（ P = 0.021） ; （3）The haplotype between rs2337980 and rs1909884 as well as the hyplotype among rs2337980, rs1909884 and rs883473 may have significant association with schizophrenia（ global P = 0. 034; global P= 0. 027）, the T-C and T-C-T hyplotype may have transmission disequilibrium with schizophrenia. Conclusion There may be association between CHRNA7 gene polymorphisms and schizophrenia, the variant allele T in rs2337980 may have a protective effect to schizophrenia.