Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis
Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis
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DOI：
10.1002/hep.510310110
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发表时间：
2000-01-01
期刊：
影响因子：
13.5
通讯作者：
Donaldson, PT
中科院分区：
文献类型：
--
作者：
Agarwal, K;Czaja, AJ;Donaldson, PT
1型自身免疫性肝炎的遗传易感性以女性为主，且与人类白细胞抗原（HLA） DRB1*0301和DRB1*0401密切相关。染色体2q33上编码细胞毒性t淋巴细胞抗原-4 （CTLA-4）的基因也可能影响自身免疫。为了确定CTLA-4外显子1腺嘌呤(A)-鸟嘌呤(G)碱基交换多态性在1型自身免疫性肝炎患者中的频率和意义，我们用聚合酶链反应检测了155名北欧高加索患者和102名种族匹配的对照组。患者的基因型分布与对照组相比有显著差异（AA = 50/155患者vs 51/102对照组；AG = 84/155患者vs 38/102对照组；GG = 21/155患者vs 13/102对照组，chi(2) = 8.94, P = 0.011），这一差异是由于患者中G等位基因明显高于对照组（105/155患者vs 51/102对照组，chi(2) = 8.34, P = 0.004，优势比= 2.12）。GG基因型与较高的平均血清天冬氨酸转氨酶水平（P = 0.03）、较高的甲状腺微体抗原抗体频率（P = 0.004）相关，在HLA DRB1*0301患者中更为常见（P = 0.02），但治疗结果不受基因型的影响，ctla - 4g等位基因在1型自身免疫性肝炎患者中更为常见，可能是第二易感等位基因。HLA-DRB1*0301与GG基因型在疾病风险方面可能存在协同作用。
Genetic susceptibility to type 1 autoimmune hepatitis is indicated by a preponderance of female subjects and strong associations with human Leukocyte antigens (HLA) DRB1*0301 and DRB1*0401. The gene encoding cytotoxic T-lymphocyte antigen-4 (CTLA-4) on chromosome 2q33 may also influence autoimmunity. To determine the frequency and significance of the exon 1 adenine (A)-guanine (G) base-exchange polymorphism for CTLA-4 in patients with type 1 autoimmune hepatitis, 155 northern European Caucasoid patients and 102 ethnically-matched control subjects were tested by polymerase chain reaction. The genotype distribution was significantly different in patients compared to controls (AA = 50/155 patients vs. 51/102 controls; AG = 84/155 patients vs. 38/102 controls; GG 21/155 patients vs. 13/102 controls, chi(2) = 8.94, P = .011), This difference was caused by a significant over-representation of the G allele in patients compared to controls (105/155 patients vs. 51/102 controls, chi(2) = 8.34, P = .004, odds ratio = 2.12). The GG genotype was associated with a significantly higher mean serum aspartate transaminase level (P = .03), greater frequency of antibodies to thyroid microsomal antigens (P = .004) and was found more commonly in patients with HLA DRB1*0301 (P = .02), Treatment outcomes, however, were not affected by the genotype, The CTLA-4 G allele is more common in patients with type 1 autoimmune hepatitis and may represent a second susceptibility allele, Furthermore, there may be synergy between the HLA-DRB1*0301 and the GG genotype in terms of disease risk.