Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy.
Department of Infectious Diseases, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.
HIV Med. 2018 Oct;19(9):597-604. doi: 10.1111/hiv.12638. Epub 2018 Jun 22.
The aim of the study was to investigate whether the rs35761398 variants of the cannabinoid receptor 2 (CB2) gene may influence the acquisition of HIV infection and the clinical presentation of HIV/hepatitis C virus (HCV) coinfection.
We compared 166 HIV/HCV-coinfected patients with 186 HCV-monoinfected patients, all with biopsy-proven chronic hepatitis (using the Ishak scoring system), naïve for anti-HCV treatment and tested for the CB2 rs35761398 polymorphism (using the TaqMan assay).
The HIV/HCV-coinfected patients were more frequently male (P < 0.002), were younger (P < 0.001), and had lower median BMI (P < 0.001) and HCV RNA (P < 0.05) and higher median aspartate aminotransferase (AST; P < 0.001), alanine aminotransferase (ALT; P < 0.001) and gamma glutamyl transferase (GGT; P < 0.001) levels than the HCV-monoinfected patients. The CB2 RR variant predominated in HIV/HCV-coinfected patients (45.8% vs. 31.2% in HCV-monoinfected patients; P < 0.001) and the CB2 QR variant in HCV-monoinfected patients (57.5% vs. 38.6% in HIV/HCV-coinfected patients; P < 0.00001), and the CB2 QQ variant was equally distributed. Focusing on patients with the CB2 QQ variant, the 26 HIV/HCV-coinfected patients, compared with the 21 HCV-monoinfected patients, showed less severe liver necroinflammation [lower histological activity index (HAI)] (P < 0.05). Of the patients with the CB2 RR variant, the 76 HIV/HCV-coinfected patients, compared with the 58 HCV-monoinfected patients, were more frequently male (P < 0.05), were younger (P < 0.001), and had a lower median body mass index (BMI; P < 0.001), a higher median AST level (P < 0.001), a higher mean HAI score (P < 0.05) and a higher rate of cases with severe steatosis (P = 0.05). In an analysis of variance (anova) of HCV/HIV-coinfected and HCV-monoinfected patient data, those with the CB2 RR variant (P = 0.003) and of male sex (P = 0.002) were more prevalent in the HCV/HIV-coinfected group.
There is the suggestion of a positive effect of the CB2 RR variant on HIV acquisition and/or spread, which is in accordance with previous in vitro observations.
本研究旨在探讨大麻素受体 2（CB2）基因的 rs35761398 变异是否可能影响 HIV 感染的获得以及 HIV/丙型肝炎病毒（HCV）合并感染的临床特征。
我们比较了 166 例 HIV/HCV 合并感染患者和 186 例 HCV 单感染患者，所有患者均经肝活检证实为慢性肝炎（采用 Ishak 评分系统），且均未接受过抗 HCV 治疗，并采用 TaqMan 检测方法检测 CB2 rs35761398 多态性。
HIV/HCV 合并感染患者中男性更常见（P<0.002），年龄更小（P<0.001），中位 BMI（P<0.001）和 HCV RNA（P<0.05）水平更低，中位天门冬氨酸氨基转移酶（AST；P<0.001）、丙氨酸氨基转移酶（ALT；P<0.001）和γ-谷氨酰转移酶（GGT；P<0.001）水平更高。HIV/HCV 合并感染患者中 CB2 RR 变异型更为常见（45.8%比 HCV 单感染患者中的 31.2%；P<0.001），而 HCV 单感染患者中 CB2 QR 变异型更为常见（57.5%比 HIV/HCV 合并感染患者中的 38.6%；P<0.00001），而 CB2 QQ 变异型分布则相当。在关注 CB2 QQ 变异型的患者中，与 21 例 HCV 单感染患者相比，26 例 HIV/HCV 合并感染患者的肝脏坏死性炎症程度较轻[较低的组织学活动指数（HAI）]（P<0.05）。在 CB2 RR 变异型患者中，与 58 例 HCV 单感染患者相比，76 例 HIV/HCV 合并感染患者更常见于男性（P<0.05），年龄更小（P<0.001），中位 BMI 更低（P<0.001），AST 水平更高（P<0.001），HAI 评分均值更高（P<0.05），且严重脂肪变性发生率更高（P=0.05）。在 HCV/HIV 合并感染和 HCV 单感染患者数据的方差分析（ANOVA）中，CB2 RR 变异型（P=0.003）和男性（P=0.002）在 HCV/HIV 合并感染组中更为常见。
CB2 RR 变异型可能对 HIV 的获得和/或传播有积极影响，这与之前的体外观察结果一致。
