Departments of Molecular Hepatology and Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Hepatol Res. 2011 Feb;41(2):151-9. doi: 10.1111/j.1872-034X.2010.00757.x.
Recently, the associations of +49A/G polymorphisms of cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene with the susceptibility to type 1 autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) have been reported; however these associations are yet to be fully elucidated. This study aimed to identify the associations of CTLA-4 gene +49A/G polymorphisms with the susceptibility to type 1 AIH and PBC by using a meta-analysis.
PubMed was searched by using the following keywords: "autoimmune hepatitis AND (polymorphism OR polymorphisms)" or "primary biliary cirrhosis AND (polymorphism OR polymorphisms)". Meta-analyses of five studies including 526 patients with type 1 AIH and 631 controls and seven studies including 1500 patients with PBC and 2345 controls were performed.
For type 1 AIH, the odds ratio (OR) of G allele was 1.26 [95% confidence interval (CI) 1.06-1.51] although G/G homozygosity was not associated with the susceptibility to type 1 AIH. On the other hand, the OR of A/A homozygosity for type 1 AIH was 0.66 (95% CI 0.50-0.86). For PBC, the OR of G allele was 1.20 (95% CI 1.06-1.34). Furthermore, G/G homozygosity was significantly associated with the susceptibility to PBC (OR 1.29, 95% CI 1.01-1.66). The OR of A/A homozygosity for PBC was 0.81 (95% CI 0.70-0.94).
This study suggests that CTLA-4 gene +49A/G polymorphisms may be associated with the susceptibility to type 1 AIH and PBC. Especially, while G/G genotype may be associated with the susceptibility to PBC, A/A genotype may be protective against type 1 AIH and PBC.
最近，细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）基因的+49A/G 多态性与 1 型自身免疫性肝炎（AIH）和原发性胆汁性肝硬化（PBC）的易感性有关；然而，这些关联尚未完全阐明。本研究旨在通过荟萃分析确定 CTLA-4 基因+49A/G 多态性与 1 型 AIH 和 PBC 易感性的关系。
使用以下关键词在 PubMed 中进行搜索：“自身免疫性肝炎 AND（多态性 OR 多态性）”或“原发性胆汁性肝硬化 AND（多态性 OR 多态性）”。对包括 526 例 1 型 AIH 患者和 631 名对照在内的 5 项研究和包括 1500 例 PBC 患者和 2345 名对照在内的 7 项研究进行荟萃分析。
对于 1 型 AIH，G 等位基因的比值比（OR）为 1.26（95%置信区间 [CI] 1.06-1.51），尽管 G/G 纯合子与 1 型 AIH 的易感性无关。另一方面，1 型 AIH 的 A/A 纯合子的 OR 为 0.66（95%CI 0.50-0.86）。对于 PBC，G 等位基因的 OR 为 1.20（95%CI 1.06-1.34）。此外，G/G 纯合子与 PBC 的易感性显著相关（OR 1.29，95%CI 1.01-1.66）。PBC 的 A/A 纯合子的 OR 为 0.81（95%CI 0.70-0.94）。
本研究表明 CTLA-4 基因+49A/G 多态性可能与 1 型 AIH 和 PBC 的易感性有关。特别是，虽然 G/G 基因型可能与 PBC 的易感性有关，但 A/A 基因型可能对 1 型 AIH 和 PBC 具有保护作用。
