Zhang Hong-xing, Li Wen-qiang, Zhang Yan, Zhao Jing-ping, Lv Lu-xian, Yang Ge
Department of Psychiatry, the Second Affiliated Hospital, Xinxiang Medical College, Xinxiang, Henan 453002 PR China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009 Feb;26(1):16-20. doi: 10.3760/cma.j.issn.1003-9406.2009.01.004.
To investigate the association of the Neuregulin 1(NRG1) gene polymorphism with schizophrenia by analyzing allele transmission in schizophrenic parent-proband trios.
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 5o 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.
For all the subjects, the genotypes of the 4 SNPs were in Hardy-Weinberg equilibrium. In all the 258 parent-proband trios, there were significant transmission disequilibrium in allelic transmission of C, A, T from rs221533, 433E1006, rs3924999 loci respectively (rs221533: chi-square was 27.45, P was 0.000; 433E1006: chi-square was 56.08, P was 0.000; rs3924999: chi-square was 10.53, P was 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: chi-square was 5.26, P was 45.08; C/C/A: chi-square was 0.026, P was 0.000). In four-marker-haplotype (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: chi-square was 10.71, P was 0.001; C/C/A/C: chi-square was 8.83, P was 0.006, C/C/A/T: chi-square was 27.00, P was 0.000). In the positive subtype of parent-proband trios, C/T/G/C hapoltype transmission was not observed.
The NRG1 gene polymorphism is significantly associated with schizophrenia in Chinese Han, especially in the positive subtype of schizophrenia.
通过分析精神分裂症患者父母-先证者三联体中的等位基因传递情况，研究神经调节蛋白1（NRG1）基因多态性与精神分裂症的关联。
采用定量实时聚合酶链反应检测258例中国汉族精神分裂症患者父母-先证者三联体中位于Nrg1基因5'端的4个单核苷酸多态性（SNP）——rs221533（C/T）、rs7820838（C/T）、433E1006（A/G）和rs3924999（C/T）的基因型。使用传递不平衡检验（TDT）程序（Genehunter软件2.0）评估NRG1基因与精神分裂症的关联。
所有受试者的4个SNP基因型均处于哈迪-温伯格平衡。在所有258个父母-先证者三联体中，rs221533、433E1006、rs3924999位点的C、A、T等位基因传递存在显著的传递不平衡（rs221533：卡方值为27.45，P值为0.000；433E1006：卡方值为56.08，P值为0.000；rs3924999：卡方值为10.53，P值为0.001）。对频率超过1%的单倍型进行分析。在三标记单倍型中，C/C/G和C/C/A（标记顺序：rs221533、rs7820838、433E1006）主要传递（C/C/G：卡方值为5.26，P值为45.08；C/C/A：卡方值为0.026，P值为0.000）。在四标记单倍型（标记顺序：rs221533、rs7820838、433E1006、rs3924999）中，C/C/G/T、C/C/A/C和C/C/A/T显示传递不平衡（C/C/G/T：卡方值为10.71，P值为0.001；C/C/A/C：卡方值为8.83，P值为0.006；C/C/A/T：卡方值为27.00，P值为0.000）。在父母-先证者三联体的阳性亚型中，未观察到C/T/G/C单倍型传递。
NRG1基因多态性与中国汉族精神分裂症显著相关，尤其是在精神分裂症的阳性亚型中。
