多发家系精神分裂症肿瘤坏死因子α基因启动子多态性与其血浆水平的关系

The relationship between tumor necrosis factor alpha gene promoter polymorphism and plasma level in schizophrenic complex families

目的探讨多发家系精神分裂症患者肿瘤坏死因子α基因启动子(TNF-αP)区-308A/G 位点基因多态性与血浆水平的关系。方法纳入51个多发精神分裂症家系(血亲同胞中有≥2例同胞符合美国精神障碍诊断与统计手册第4版精神分裂症诊断标准的患者,且血亲父母健在)222人完成遗传学研究用诊断会谈及遗传学研究用家属会谈表;分为患者组(98例)、父母组(94名)及正常同胞组(30名)。非血亲健康对照组(40名,以下简称对照组)。用聚合酶链反应特异序列引物法检测基因型。用酶联免疫吸附法检测 TNF-α血浆浓度。统计分析采用 x^2检验、t 检验、传递不平衡检验及关联分析。结果(1)患者、父母、正常同胞及对照组基因型均以 G/G 为多,分别为80%、81%、90%及85%,A/G 分别为20%、19%、10%及15%,未检出 A/A 基因型;等位基因 A 的频度分别为10%、10%、5%及8%;等位基因 G 分别为90%、90%、95%及92%;4组间基因型及等位基因频度分布的差异均无统计学意义(P>0.05)。(2)TNF-αP区-308A 等位基因在精神分裂症患者中存在传递不平衡性(McNemar x^2=3.85,P<0.05),相对风险分析(RR)呈负相关(RR=0.44,X_(RR)~2=3.846,P<0.05)。(3)患者、父母、正常同胞及对照组 G/G 型 TNF-α血浆浓度分别为(61±29)ng/L、(68±29)ng/L、(80±23)ng/L 和(73±32)ng/L;A/G 型分别为(64±21)ng/L、(79±40)ng/L、(95±46)ng/L和(81±35)ng/L;各组两型间 TNF-α浓度的差异均无统计学意义(P 均>0.05)。结论 TNF-αP区-308A 等位基因在精神分裂症患者中的传递频率较低;-308A 等位基因与精神分裂症存在相关性,但与 TNF-α血浆水平变化无直接关系。

Objects The aim of this study was to investigate the relationships between the tumor necrosis factor alpha （TNFalpha）- G308A gene promoter polymorphism and plasma levels in schizophrenia. Methods Fifty-one pedigrees with at least two siblings affected schizophrenia and biological parents were recruited, and another 40 healthy persons were involved as normal controls. The subjects were assessed with the Chinese versions of the Diagnosis Interview for Genetics Study and the Family Interview for Genetic Study. The gene was genotyped with polymerase chain reaction sequence-specific primers, and TNF-α plasma level detected with enzyme linked immunosorbent assay. The chi-square test, t test, the transmission disequilibrium test and association analysis were conducted. Results （1） There were no significant differences in the genotypes of G/G and G/A and the distributions of allele A and G among the patients, their parents, their non-affected siblings and normal controls （P 〉 0. 05）. （2） The - 308A allele had transmission disequilibrium （ McNemar X2 = 3.85, P 〈 0. 05 ） in schizophrenic patients, and negative association between the - 308A allele and schizophrenia was found （RR = 0. 44, XRR^2 = 3. 846, P 〈 0. 05 ）. （3） Within each group of patients, their parents, their non-affected siblings and normal controls, there were no significant differences in the plasma levels of TNF-α between ones with genotype G/G and A/G （ P 〉0. 05 ）. Conclusion The TNF-α-p -308A allele may be associated with schizophrenia, with no direct relationship to plasma TNF-αlevels.