Xu Enbin, Cao Hailian, Lin Liming, Liu Honglong
Department of Gastroenterology, No.404 Hospital of People's Liberation Army, Weihai, Shandong, China.
PLoS One. 2017 Apr 27;12(4):e0176471. doi: 10.1371/journal.pone.0176471. eCollection 2017.
Previous studies have found that the polymorphisms of tumor necrosis factor-α induced protein 3 (TNFAIP3) were associated with several autoimmune diseases. However, the role of TNFAIP3 polymorphisms in type-1 autoimmune hepatitis (AIH-1) remained unclear. The present study aimed to clarify the association of TNFAIP3 polymorphisms with AIH-1 risk in a Chinese Han population. The TaqMan SNP genotyping assay was used to determine the distribution of TNFAIP3 polymorphisms in 432 AIH-1 patients and 500 healthy controls. The association of TNFAIP3 polymorphisms and clinical characteristic was further evaluated. Five TNFAIP3 polymorphisms (rs2230926, rs5029939, rs10499194, rs6920220, rs582757) were analyzed in the present study. No significant association could be observed between rs2230926, rs5029939, rs6920220, rs582757 and the susceptibility to AIH-1 in Chinese Han population. Compared with wild-type genotype CC at rs10499194, individuals carrying CT genotype had a significantly increased risk for developing AIH-1 (OR = 2.32, 95%CI 1.44-3.74). Under a dominant model, CT/TT carriers have a 140% increased risk of AIH-1 than CC carriers (OR = 2.40, 95%CI 1.50-3.87). The rs10499194 T allele was also found to be significantly associated with AIH-1 risk (OR = 2.41, 95%CI 1.51-3.82). In addition, higher serum ALT, AST levels and more common cirrhosis were observed in AIH-1 patients with T allele (CT/TT) than those with CC genotype. In conclusion, TNFAIP3 rs10499194 T allele and CT genotype were associated with an increased risk for AIH-1, suggesting rs10499194 polymorphism as a candidate of susceptibility locus to AIH-1.
既往研究发现，肿瘤坏死因子-α诱导蛋白3（TNFAIP3）的多态性与多种自身免疫性疾病相关。然而，TNFAIP3多态性在1型自身免疫性肝炎（AIH-1）中的作用仍不明确。本研究旨在阐明TNFAIP3多态性与中国汉族人群AIH-1发病风险的关联。采用TaqMan SNP基因分型检测法确定432例AIH-1患者和500例健康对照中TNFAIP3多态性的分布。进一步评估TNFAIP3多态性与临床特征的关联。本研究分析了5个TNFAIP3多态性位点（rs2230926、rs5029939、rs10499194、rs6920220、rs582757）。在中国汉族人群中，未观察到rs2230926、rs5029939、rs6920220、rs582757与AIH-1易感性之间存在显著关联。与rs10499194位点的野生型基因型CC相比，携带CT基因型的个体发生AIH-1的风险显著增加（OR = 2.32，95%CI 1.44-3.74）。在显性模型下，CT/TT携带者发生AIH-1的风险比CC携带者高140%（OR = 2.40，95%CI 1.50-3.87）。还发现rs10499194的T等位基因与AIH-1风险显著相关（OR = 2.41，95%CI 1.51-3.82）。此外，携带T等位基因（CT/TT）的AIH-1患者血清ALT、AST水平更高，肝硬化更常见。总之，TNFAIP3 rs10499194的T等位基因和CT基因型与AIH-1风险增加相关，提示rs10499194多态性可能是AIH-1的一个易感基因座候选位点。
