Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario "Gregorio Marañón", Madrid, Spain.
Sci Rep. 2017 Jan 31;7:41516. doi: 10.1038/srep41516.
The mechanisms involved in the chronic hepatitis C progression are incompletely understood. The aim was to analyze the association between 2'5'oligoadenylate synthetase 1,2 and 3 (OAS1-3) and myxovirus resistance proteins 1 (Mx1) polymorphisms and severity of liver disease in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients. We performed a cross-sectional study in 219 patients that underwent a liver biopsy. DNA genotyping for Mx1 (rs469390), OAS1 (rs2285934), OAS2 (rs1293762) and OAS3 (rs2010604) was performed by using GoldenGate assay. The outcome variables ion liver biopsy were: (i) significant fibrosis (F ≥ 2); (ii) moderate activity grade (A ≥ 2). Additive model of inheritance for genetic association test was used. The likelihood of having significant fibrosis (F ≥ 2) was lower in patients carrying OAS2 rs1293762 A allele [adjusted odds ratio (aOR) = 0.51; p = 0.040]. Besides, the likelihood of having moderate activity grade (A ≥ 2) was higher in patients carrying Mx1 rs464397 C allele (aOR = 1.63; p = 0.028) and Mx1 rs469390 G allele (aOR = 1.97; p = 0.005), while it was lower in patients carrying OAS1 rs2285934 A allele (aOR = 0.64; p = 0.039) and OAS2 rs1293762 A allele (aOR = 0.41; p = 0.009). In conclusion, Mx1 and OAS1-2 polymorphisms were associated with the severity of liver disease in HIV/HCV-coinfected patients, suggesting a significant role in the progression of hepatic fibrosis.
慢性丙型肝炎进展的机制尚不完全清楚。本研究旨在分析 2′5′寡聚腺苷酸合成酶 1、2 和 3(OAS1-3)和抗黏液病毒蛋白 1(Mx1)多态性与人类免疫缺陷病毒(HIV)/丙型肝炎病毒(HCV)合并感染患者肝病严重程度之间的关系。我们对 219 例接受肝活检的患者进行了横断面研究。采用 GoldenGate 检测法对 Mx1(rs469390)、OAS1(rs2285934)、OAS2(rs1293762)和 OAS3(rs2010604)的 DNA 基因型进行检测。肝活检的转归变量为:(i)显著纤维化(F≥2);(ii)中重度活动度分级(A≥2)。采用遗传关联检验的加性模型进行分析。携带 OAS2 rs1293762 A 等位基因的患者发生显著纤维化(F≥2)的可能性较低(调整优势比[aOR] = 0.51;p=0.040)。此外,携带 Mx1 rs464397 C 等位基因的患者发生中重度活动度分级(A≥2)的可能性较高(aOR=1.63;p=0.028)和 Mx1 rs469390 G 等位基因(aOR=1.97;p=0.005),而携带 OAS1 rs2285934 A 等位基因的患者(aOR=0.64;p=0.039)和 OAS2 rs1293762 A 等位基因(aOR=0.41;p=0.009)的可能性较低。综上所述,Mx1 和 OAS1-2 多态性与 HIV/HCV 合并感染患者的肝病严重程度相关,提示其在肝纤维化进展中具有重要作用。