肿瘤坏死因子基因与精神分裂症的传递不平衡研究

A transmission disequllibrhnn study of the tumor necrosis factor genes in schizophrenia

目的探讨肿瘤坏死因子-α（TNF-α）基因和肿瘤坏死因子-β（TNF-β）基因与精神分裂症的关系。方法收集172个广东潮汕地区的精神分裂症核心家系，将172例精神分裂症患者分为偏执型（96例）和非偏执型（76例），用聚合酶链反应-限制性片段长度多态性方法，检测所有研究对象的TNF-α的3个多态性位点（-C863A、-G308A、-G238A）和TNF-β＋A252G位点的等位基因频率和基因型频率，并进行传递不平衡检验（TDT）。结果（1）单位点TDT检验，TNF-β＋A252G位点杂合子父母过多地传递等位基因G给患者（X^2=5．49，Pc〈0．05），而TNF-α的3个多态性位点（-C863A、-G308A、-G238A）均未发现传递不平衡。（2）多位点联合进行单体型分析，未显示在精神分裂症核心家系中存在传递不平衡；但在96个偏执型精神分裂症核心家系中，有一种常见单体型[（-863C，-308G，-238G，＋252G）；X2=7．20，Pc〈0．05]存在偏向传递。结论在广东潮汕人群中，TNF-α和TNF-β基因与精神分裂症可能存在某些关联，该基因可能是偏执型精神分裂症的易感基因。

Objective To investigate the association between the tumor necrosis factor-α （TNF-α） and-β （TNF-β） gene with schizophrenia. Methods The genotypes and alldie frequencies of the three polymorphism loci of TNF-α gene （ -C863A, -G308A, -G238A） and the TNF-β ＋ A252G locus were examined in 172 schizophrenic trios （96 with paranoid and 76 with non- paranoid type） collected from Chaoshan region, using the transmission/disequilibrium test （TDT）. Results （ 1 ） The one-marker TDT results showed that the allele G （X^2 =5.49, Pc 〈0. 05） of the TNF-β ＋ A252G was over-transferred in the heterozygous parents to patients, whereas the three polymorphism loci in TNF-α gene did not show biased transmission. （2） The multi-marker haplotypes analysis results showed that there were no haplotypes existed transmission disequilibrium in schizophrenic trios. In 96 schizophrenic trios with paranoid type, multi-maker haplotypes analysis showed that there were main haplotypas of [ （ -863C, -308G, -238G and ＋ 252G） ; X^2 = 7.20, Pc 〈 0.05 ] which over-transferred. Condusion The TNF-α gene and the TNF-β gene may be associated with schizophrenia in the Chaoshan population, which may confer susceptibility to schizophrenia paranoid type.