肿瘤坏死因子α基因多态性与中国人自身免疫肝病相关性研究

目的 探讨肿瘤坏死因子α(TNFα)启动子基因多态性与中国人自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)发病的相关性。方法 采用序列特异性聚合酶链式反应方法分析49例AIH、58例PBC患者外周血单核细胞基因组DNA TNFα启动子308、-238G／A基因多态性，并与160例正常对照组比较。结果 正常对照组中国人与白种人TNFα*2携带率差异较大。虽然从百分率上可以看出中国人PBC患者TNFα*2携带率低于正常对照组(10．34％与16.88％)，但统计学上两者差异无显著性，TNFα-238位基因多态性分布也与正常对照组差异无显著性；AIH患者TNFα启动子-308、-238G／A基因多态性均与正常人差异无显著性。结论 不同人种自身免疫肝病的免疫相关基因不同，中国人AIH、PBC与TNFα启动子基因的多态性间不存在基因连锁关系。

Genetic association of tumor necrosis factor (TNF)-alpha polymorphisms with primary biliary cirrhosis and autoimmune liver diseases in a Chinese population

Objective Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two autoimmune diseases of unknown etiology. Genetic factors appear to be involved in the pathogenesis of both diseases. Tumor necrosis factor (TNF)-alpha is one of the proinflammatory cytokines and immunomodulators, and is implicated in the pathogenesis of AIH and PBC. In this study, we studied the association between Chinese patients with AIH, PBC and the polymorphisms in promoter-region polymorphisms of the TNF-alpha gene at position -308 and -238. Methods We have investigated four candidate gene loci in 49 patients with AIH, 58 patients with PBC, and 160 healthy controls. The polymorphisms were assessed by the PCR specifically for the single-nucleotide polymorphisms. Results We found the difference in the TNF-alpha gene at position -308 genotype distributions between Chinese health controls and Caucasian health controls. Although the percent of TNF-alpha*2 was decrease on PBC patient group (10.34% vs. 16.88%), there was no significant difference between PBC patients and health control in the Chinese. There were also no significant differences between AIH and health control on the TNF-alpha gene at position -308 and -238. Conclusion Our findings suggest that the TNF-alpha promoter-region polymorphisms distribution is different between differe of ethnic groups; there are no genetic links of the TNF-alpha promoter-region polymorphisms to AIH and PBC in Chinese.