体内证据表明，大麻素受体 2-63RR 变体与 HIV 感染的获得和/或扩展有关。
In vivo evidence that the cannabinoid receptor 2-63 RR variant is associated with the acquisition and/or expansion of HIV infection.
机构信息
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.
出版信息
HIV Med. 2018 Oct;19(9):597-604. doi: 10.1111/hiv.12638. Epub 2018 Jun 22.
OBJECTIVES
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.
METHODS
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).
RESULTS
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.
CONCLUSIONS
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.
目的
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。
方法
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。
结果
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。
结论
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。
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