McIlroy Dorian, Théodorou Ioannis, Ratziu Vlad, Vidaud Dominique, Pellet Philippe, Debré Patrice, Poynard Thierry
Laboratoire d'Immunologie Cellulaire et Tissulaire bService de Gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France.
Eur J Gastroenterol Hepatol. 2005 Oct;17(10):1081-8. doi: 10.1097/00042737-200510000-00012.
Hepatocytes are susceptible to FAS-mediated apoptosis. The impact of polymorphisms in the FAS gene on histopathological features of HCV infection was therefore investigated.
DESIGN/METHODS: Three single-nucleotide polymorphisms in the FAS promoter were assessed in 190 patients with chronic hepatitis C. Associations between FAS haplotypes and fibrosis stage and activity grade were tested by univariate and multivariate analyses.
While there was no correlation between FAS promoter genotype and fibrosis stage, patients carrying the GCA haplotype (P=0.03, Fisher's exact test) and those homozygous for the GTG haplotype (P = 0.06) tended to have lower activity scores. Logistic regression showed that these associations were independent of patient age, sex and alcohol consumption. In a logistic regression model incorporating only male gender (odds ratio 2.1, 95% confidence interval 1.1-4.1 P = 0.04), the presence of the GCA haplotype (OR 0.31 95% CI 0.13-0.78 P = 0.01), and GTG homozygosity (OR 0.26 95% CI 0.08-0.83 P = 0.02), all three factors were independently correlated with activity grade. Furthermore, the GTG haplotype appeared to have lower promoter activity than the wild type GTA haplotype in a hepatocellular carcinoma cell line.
Genetic polymorphism in the FAS gene may account for some of the histopathological variability in chronic hepatitis C.
肝细胞易受FAS介导的凋亡影响。因此，研究了FAS基因多态性对丙型肝炎病毒（HCV）感染组织病理学特征的影响。
设计/方法：对190例慢性丙型肝炎患者评估FAS启动子中的三个单核苷酸多态性。通过单因素和多因素分析测试FAS单倍型与纤维化阶段和活动度分级之间的关联。
虽然FAS启动子基因型与纤维化阶段之间无相关性，但携带GCA单倍型的患者（P=0.03，Fisher精确检验）和GTG单倍型纯合子患者（P = 0.06）的活动度评分往往较低。逻辑回归显示，这些关联独立于患者年龄、性别和饮酒量。在仅纳入男性性别（比值比2.1，95%置信区间1.1 - 4.1，P = 0.04）、GCA单倍型的存在（OR 0.31，95% CI 0.13 - 0.78，P = 0.01）和GTG纯合性（OR 0.26，95% CI 0.08 - 0.83，P = 0.02）的逻辑回归模型中，所有这三个因素均与活动度分级独立相关。此外，在一种肝癌细胞系中，GTG单倍型的启动子活性似乎低于野生型GTA单倍型。
FAS基因的遗传多态性可能是慢性丙型肝炎组织病理学变异性的部分原因。
