精神分裂症与神经调节素1、G72及G-蛋白信号转导调节子4基因的关联研究

Association study between schizophrenia and NRG1, G72, RGS4 polymorphisms

目的 探索神经调节素1（NRG1）、G72、G-蛋白信号转导调节子4（RGS4）基因变异的独立或联合作用与精神分裂症的关联。方法 采用酶切或测序方法,对315例精神分裂症患者和347例正常对照者NRG1、G72、RGS4基因的13个单核苷酸多态性（SNPs）位点进行基因型检测和遗传关联分析。应用Lo-gistic回归分析和风险或保护基因型分层后卡方检验评估三基因的交互作用。结果 单位点关联分析发现,NRG1的5个SNPs、G72的1个SNP、RGS4的2个SNPs与精神分裂症关联（P〈0.05）。Logistic回归分析构建了三个基因交互作用模型,各自变量的OR分别为：nrg1=3.58,rgs4=1.24,g72_rs947267=1.45,nrg1＊rgs4=3.03,nrg1＊g72_rs947267=1.06。应用基因型分层后卡方检验表明,三基因存在协同风险效应（OR=2.35～4.05;P〈0.05）。结论 NRG1、G72及RGS4基因的单独或交互作用与精神分裂症关联。

Objective To examine the independent and interactive roles of neuregulin 1 （NRG1）, G72, and the regulator of G-protein signaling-4 （RGS4） in schizophrenia. Methods Three hundred and fifteen unrelated schizophrenia patients and 347 healthy control subjects were recruited. Genotyping for 13 single nucleotide polymorphisms （SNPs） were examined using polymerase chain reaction-based restriction fragment length polymorphism or direct sequencing. Case-control association analysis was performed. To illustrate this interaction, we also made the logistic regression analysis and calculated the odd ratios （ORs） for risk or protective genotypes of above three candidate genes. Results Of seven polymorphic markers in the NRG1 gene, five showed strong evidence of association （ P〈 0.05 ）. SNP rs947267 at G72 locus and two SNPs at RGS4 gene were also associated with schizophrenia （P〈0.05）. A logistic regression model examined significant gene-gene interactions among above three genes （OR values of independent variables： nrgl = 3.58, rgs4 = 1.24, g72_rs947267 = 1.45, nrgl ＊ rgs4 = 3.03,nrgl ＊ g72_rs947267 = 1.06）. Such results were further verified by using the OR calculation of different combinations of genotypes at NRG1 and G72 or RGS4. Conclusions The individual and interactive effect of polymorphisms at NRG1, G72, and RGS4 genes were associated with schizophrenia.