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烟碱型乙酰胆碱受体基因多态与早发性精神分裂症的关联研究 被引量:5

Association study of neuronal nicotinic acetylcholine receptor subunit genes with early onset schizophrenia
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摘要 目的探讨烟碱型乙酰胆碱受体基因多态在早发性精神分裂症发生中的作用。方法采用TaqMan荧光探针基因分型技术对421例早发性精神分裂症患者和598例健康对照者的α3、α4、α7、α5烟碱型乙酰胆碱受体基因(nicotinic acetylcholine receptor subunit gene)即CHRNA3(rs1317286)、CHRNA4(rs1044396)、CHRNA7(rs6494212)及CHRNA5(rs16969968,rs684513)基因多态位点进行基因分型,分析这些位点与早发性精神分裂症的关联及其与发病年龄的关系,并进一步分析基因与基因的交互作用。结果单位点分析显示所有位点的差异比较结果无统计学意义。Kaplan-Meier生存分析显示携带rs1317286G等位基因的患者发病年龄晚于不携带rs1317286G等位基因的患者[发病年龄分别为(15.5±0.33)岁和(15.1±0.14)岁,P=0.010]。CHRNA5基因的两个单核苷酸多态位点(single nucleotide polymorphisms,SNPs)组成的单体型也显示不与早发性精神分裂症关联。进一步的基因交互作用分析显示rs1044396、rs6494212及rs684513联合作用模式可能与精神分裂症相关(P=0.0007)。结论 CHRNA3(rs1317286)位点可能与精神分裂症的发病年龄相关;rs1044396、rs6494212及rs684513基因的联合作用模式可能与早发性精神分裂症有关。 Objective To investigate the relationship between neuronal nicotinic acetylcholine receptor subunit genes polymorphisms and early onset schizophrenia. Method Five single nucleotide polymorphisms (SNPs of CHR- NA7,CHRNAd, CHRNA3 and CHRNAS) were analyzed in a sample of 421 early onset schizophrenic patients with onset before age 18 and 598 healthy controls. The five markers were genotyped by using the TeqMan fluorogenic detection method with the ABI7900. The association of the locus with early onset schizophrenia and age of onset was analyzed. Results There were no significant differences in the frequencies of the genotypes and alleles of the polymorphisms between cases and normal controls (P〉0.05). The age at onset was significantly associated with the G allele of rs1317286 (P=0.010).The haplotype constructed by markers of CHRNA5 were not associated with schizophrenia. The interaction analysis reveal a significant association between models made up by rs1044396, rs6494212, rs684513 and early onset schizophrenia (P=0.0007). Conclusions The age at onset is significantly associated with the G allele of rs1317286. There is a significant association between models made up by rs1044396, rs6494212 and rs684513 and early age schizophrenia.
出处 《中国神经精神疾病杂志》 CAS CSCD 北大核心 2013年第1期17-22,共6页 Chinese Journal of Nervous and Mental Diseases
基金 "重大新药创制"精神药物新药临床评价研究技术平台(编号:2012ZX09303-003) 上海市精神卫生中心科研基金(编号:2010-YJ-10) 上海市精神卫生中心科研基金(编号:2010-YJ-10)
关键词 早发性精神分裂症 乙酰胆碱受体基因 多态性 关联分析 Early onset schizophrenia Nicotinic acetylcholine receptor Polymorphism Association study
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同被引文献29

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