CTLA-4 gene polymorphism confers susceptibility to primary biliary cirrhosis
CTLA-4 gene polymorphism confers susceptibility to primary biliary cirrhosis
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DOI：
10.1016/s0168-8278(00)80213-5
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发表时间：
2000-04-01
影响因子：
25.7
通讯作者：
Bassendine, MF
中科院分区：
文献类型：
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作者：
Agarwal, K;Jones, DEJ;Bassendine, MF
背景/目的：原发性胆汁性肝硬变(PBC)是一种自身免疫性淤胆性肝病，被认为是通过遗传和环境因素的复杂相互作用而发展起来的。其特点是T细胞介导的非化脓性破坏性胆管炎。细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因是PBC的候选易感基因，位于染色体2q33上(命名为IDDM12)，与1型糖尿病和自身免疫性甲状腺疾病的易感性有关。结果：PBC患者的G/A和G/G基因分型频率明显高于对照组(G/A分别为53%和40%；G/G：18.5%vs10.5%，优势比(OR)=2.45[95%可信区间1.6~3.7]，p=0.00006，chi(2)=19.4。同样，等位基因频率也有显著差异(G编码17密码子丙氨酸，PBC0.45与对照组0.305：OR=1.9[1.4-2.5]，p
Background/Aim: Primary biliary cirrhosis (PBC) is an autoimmune cholestatic liver disease thought to develop through a complex interaction of genetic and environmental factors. It is characterised by T-cell-mediated non-suppurative destructive cholangitis. We have studied the polymorphic cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene, which encodes a molecule that is a vital negative regulator of T-cell activation, as a candidate susceptibility locus for PBC, This gene on chromosome 2q33 (designated IDDM12) is associated with susceptibility to both type 1 diabetes and autoimmune thyroid disease.Methods: The CTLA-4 exon 1 polymorphism (A/G encoding for threonine or alanine, respectively) was genotyped via polymerase chain reaction in 200 Caucasoid PBC patients and 200 non-related geographically matched Caucasoid controls.Results: There was significant overrepresentation of the G/A and G/G genotypes in PBC patients compared to controls (G/A 53% vs 40%; G/G: 18.5% vs 10.5%, Odds Ratio (OR)=2.45 [95% CI 1.6-3.7], p= 0.00006, chi(2)=19.4). Likewise, there was a significant difference in allele frequencies (G encoding alanine at codon 17, PBC 0.45 vs controls 0.305: OR=1.9 [1.4-2.5], p