Li Shan, Huang Xiamei, Zhong Huizhi, Chen Zhiping, Peng Qiliu, Deng Yan, Qin Xue
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People's Republic of China.
J Genet. 2013 Dec;92(3):617-28.
Epidemiological studies have evaluated the association between tumour necrosis factor alpha (TNF-α)- 308G/A and (TNF-α)- 238G/A polymorphisms, and the risk of autoimmune liver disease (AILD), yet the results are conflicting. To derive a more precise estimation of the relationship, we performed this meta-analysis. A systematic review was conducted to identify all eligible studies of TNF-α polymorphisms and AILD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association between the two TNF-α polymorphisms and AILD risk. A total of 15 eligible studies were identified. Overall, positive associations of -308G/A polymorphism with AILD risk were found (A vs G allele: OR =1.45, 95%CI = 1.13- 1.86; AA vs GG: OR = 2.74, 95%CI = 1.51- 4.96; GA vs GG: OR = 1.46, 95%CI = 1.11- 1.92;dominant model: OR = 1.57, 95%CI = 1.18- 2.10; recessive model: OR = 2.22, 95%CI = 1.31- 3.76). In subgroup analysis by ethnicity, a significantly higher risk was found in Caucasians. In subgroup analysis by AILD category, significant association was observed in autoimmune hepatitis and primary sclerosing cholangitis, especially in Caucasians. Patients carrying TNF-α-238A allele had a slightly decreased risk of developing AILD (OR = 0.65, 95%CI = 0.48- 0.87). However, we found both TNF-α polymorphisms were not associated with primary biliary cirrhosis risk, even in subgroup analysis. Our meta-analysis suggests that the TNF-α-308G/A and -238G/A polymorphisms may contribute to AILD susceptibility in Caucasians,especially for autoimmune hepatitis and primary sclerosing cholangitis. Nevertheless, we found both TNF-α polymorphisms were unlikely to be associated with the risk of primary biliary cirrhosis
流行病学研究评估了肿瘤坏死因子α（TNF-α）-308G/A和（TNF-α）-238G/A基因多态性与自身免疫性肝病（AILD）风险之间的关联，但其结果相互矛盾。为了更精确地估计两者之间的关系，我们进行了这项荟萃分析。我们进行了一项系统评价，以确定所有关于TNF-α基因多态性与AILD风险的符合条件的研究。我们使用比值比（OR）及95%置信区间（CI）来评估两种TNF-α基因多态性与AILD风险之间关联的强度。共确定了15项符合条件的研究。总体而言，发现-308G/A基因多态性与AILD风险呈正相关（A等位基因与G等位基因：OR = 1.45，95%CI = 1.13 - 1.86；AA与GG：OR = 2.74，95%CI = 1.51 - 4.96；GA与GG：OR = 1.46，95%CI = 1.11 - 1.92；显性模型：OR = 1.57，95%CI = 1.18 - 2.10；隐性模型：OR = 2.22，95%CI = 1.31 - 3.76）。在按种族进行的亚组分析中，白种人的风险显著更高。在按AILD类别进行的亚组分析中，自身免疫性肝炎和原发性硬化性胆管炎中观察到显著关联，尤其是在白种人中。携带TNF-α -238A等位基因的患者发生AILD的风险略有降低（OR = 0.65，95%CI = 0.48 - 0.87）。然而，我们发现即使在亚组分析中，两种TNF-α基因多态性均与原发性胆汁性肝硬化风险无关。我们的荟萃分析表明，TNF-α -308G/A和-238G/A基因多态性可能导致白种人易患AILD，尤其是自身免疫性肝炎和原发性硬化性胆管炎。然而，我们发现两种TNF-α基因多态性均不太可能与原发性胆汁性肝硬化风险相关。
