Unidade de Tireóide - Laboratório de Endocrinologia Celular e Molecular - LIM 25 Disciplina de Endocrinologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Liver Int. 2012 May;32(5):803-8. doi: 10.1111/j.1478-3231.2011.02694.x. Epub 2011 Dec 4.
Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation.
To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings.
We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. -318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer.
Eight AT repetitions in 3'UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62).
CTLA-4 gene polymorphisms were associated to HCV-infection. Eight AT repetitions were more prevalent in HCV-infected subjects. -318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3'UTR region favoured severe necroinflammatory activity scores in liver biopsies.
细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）作为 T 细胞介导的免疫反应的负调节剂发挥作用。与 CTLA-4 基因多态性相关的分子变化可能会降低其抑制和控制淋巴细胞增殖的能力。
评估慢性丙型肝炎病毒（HCV）感染患者 CTLA-4 基因多态性的频率，并与临床和组织学发现相关联。
我们前瞻性选择了 112 例 HCV 感染患者和 183 例健康对照者进行评估。分析了临床和肝组织学数据。通过 PCR-RFLP 研究了 -318C > T、A49G 和 CT60 CTLA-4 单核苷酸多态性（SNP），通过毛细管电泳在自动测序仪中通过 DNA 片段分析研究了 AT（n）多态性。
在 HCV 感染患者中，3'UTR 区域的 8 个 AT 重复更为频繁。我们发现-318C 和 +49G 与 HCV 基因型 3 呈正相关（P=0.008，OR 9.13，P=0.004，OR 2.49），与 HCV 基因型 1 呈负相关（P=0.020，OR 0.19，P=0.002，OR 0.38）。等位基因+49G 也与丙氨酸氨基转移酶比值>3（qALT，P=0.034，qAST，P=0.041）相关。CT60 SNP 的等位基因 G 也与 qAST>3（P=0.012）相关。3'UTR 区域中 AT 重复次数的增加与肝活检中的严重坏死性炎症活动评分呈正相关（P=0.045，OR 4.62）。
CTLA-4 基因多态性与 HCV 感染相关。在 HCV 感染患者中，8 个 AT 重复更为常见。-318C 和+49G 等位基因与基因型 1 和 3 感染相关，3'UTR 区域中 AT 重复次数的增加有利于肝活检中的严重坏死性炎症活动评分。
