Neuregulin 1基因多态性与中国汉族精神分裂症关联分析  

Association analysis of neuregulin 1 gene polymorphism with schizophrenia in Chinese Han population

作　　者：张红星[1,2] 李文强[1] 张燕[1] 赵靖平[2] 吕路线[1] 杨鸽[1] 

机构地区：[1]新乡医学院第二附属医院河南省精神病院,河南省新乡市453002 [2]中南大学湘雅二医院精神卫生研究所

出　　处：《中华医学遗传学杂志》2009年第1期16-20,共5页Chinese Journal of Medical Genetics

基　　金：“十五”科技攻关资助项目（2004BA720A22）;河南省重点科技攻关项目（072102310013,082102310081）

摘　　要：目的探讨Neuregulin1（NRG1）基因多态性与精神分裂症的关联。方法在258个中国汉族精神分裂症核心家系（患者及其亲生父母）中，应用实时定量PCR技术检测位于NRG1基因5’端的4个单核苷酸多态（single nucleotide polymorphism，SNP）位点：rs221533（C／T）、rs7820838（C／T）、433E1006（A／G）和rs3924999（C／T），进行基因分型，应用传递不平衡检测（transmission disequilibrium test，TDT）分析等位基因传递情况，分析该基因与精神分裂症易感性的关联。结果在258个中国汉族核心家系中，rs221533、433E1006、rs3924999三个SNP均存在有统计学意义的传递不平衡，优先传递的等位基因分别是：C、A、T（rs221533：x^2=27．45，P=0．000；433E1006：x^2=56．08，P=0．000；rs3924999：x^2=10．53，P=0．001）。rs7820838未检到不平衡传递（x^2=3．31，P=0．081）。频率大于l％单倍型进行分析，rs221533-rs7820838～433E1006联合分析，单倍型C／C／G和C／C／A优先传递（C／C／G：x^2=5．26，P=45．08；C／C／A：x^2=0．026，P=0．000）；rs221533rs7820838—433E1006-rs3924999联合分析，单倍型C／C／G／T、C／C／A／C和C／C／A／T优势传递（C／C／G／W：x^2=10．71，P=0．001；C／C／A／C：x^2==8．83，P=0．006、C／C／A／T：x^2=27．00，P=0．000）。213个阳性亚型的精神分裂症核心家系中传递不平衡得出基本一致的结果。结论Nrg1基因多态性与中国汉族人群精神分裂症存在关联，尤其是支持与阳性亚型精神分裂症存在关联。Objective To investigate the association of the Neuregulin 1（ NRG1 ）gene polymorphism with schizophrenia by analyzing allele transmission in schizophrenic parent proband trios. Methods Quantitative real-time PCR was used to check the genotypes of four SNPs-rs221533（C/T）, rs7820838（C/ T）, 433E1006 （A/G） and rs3924999（C/T）, located at the 5＇ terminus of the NRG1 gene, in 258 Chinese Han schizophrenic parent-proband trios. The transmission disequilibrium test （TDT） program （Genehunter software 2.0） was used to evaluate the association of the NRG1 gene with schizophrenia. Results For all the subjects, the genotypes of the 4 SNPs were in Hardy-Weinberg equilibrium. In all the 258 parentproband trios, there were significant transmission disequilibrium in allelic transmission of C, A, T from rs221533, 433E1006, rs3924999 loci respectively （rs221533： x^2= 27. 45, P=0. 000; 433E1006： x^2= 56.08, P=0.000;rs3924999： x^2 =10. 53,P=0. 001）. Haplotype was analyzed at frequency exceeding 1%. In three-marker-haplotype, C/C/G and C/C/A （marker order： rs221533, rs7820838, 433E1006） transmitted predominantly（C/C/G：x^2 =5.26,P=45.08;C/C/A： x^2 =0. 026,P=0. 000）. In four-markerhaplotype（marker order： rs221533, rs7820838, 433E1006, rs3924999）, C/C/G/T, C/C/A/C and C/C/ A/T showed transmission disequilibrium （C/C/G/T： x^2 = 10. 71, P = 0. 001 ; C/C/A/C： x^2 = 8.83, P= 0.006, C/C/A/T： x^2=27.00, P=0.000）. In the positive subtype of parent-proband trios, C/T/G/C hapoltype transmission was not observed. Conclusion The NRG1 gene polymorphism is significantly associated with schizophrenia in Chinese Han, especially in the positive subtype of schizophrenia.

关 键 词：精神分裂症 NEUREGULIN 1基因 遗传多态性 传递不平衡分析 关联分析 

分 类 号：R686[医药卫生—骨科学]