Department of Mental Health and Public Medicine, Second University of Naples, Naples, Italy.
Internal Medicine and Hepatology, Second University of Naples, Naples, Italy.
Clin Gastroenterol Hepatol. 2014 Feb;12(2):334-40. doi: 10.1016/j.cgh.2013.05.008. Epub 2013 May 22.
BACKGROUND & AIMS: The cannabinoid receptor 2 (CB2) has been implicated in liver disease. The single-nucleotide polymorphism rs35761398 in cannabinoid receptor 2 gene (CNR2), which encodes the CB2, substitutes glutamine (Q) 63 with arginine (R), and reduces the function of the gene product. We investigated the effects of CNR2 rs35761398 in patients with hepatitis C virus (HCV) infection.
We studied 169 consecutive patients with asymptomatic chronic hepatitis (tested positive for anti-HCV and HCV RNA) at 2 liver units in southern Italy. First, liver biopsy samples were collected from July 2009 through December 2011. All patients were naive to antiviral therapy; CNR2 genotype was determined by polymerase chain reaction analysis.
Patients with the CB2-63 QQ variant had higher serum levels of aminotransferase than those with the CB2-63 QR or RR variants; they also had higher histologic activity index (HAI) scores (8.6 ± 3.8) than patients without the CB2-63 RR variant (5.3 ± 3.6; P < .005) or those with the CB2-63 QR variant (5.8 ± 3.3; P < .001). Patients with the different variants of CNR2 did not differ in fibrosis stage or steatosis score. Moderate or severe chronic hepatitis (HAI score, >8) was identified more frequently (55.5%) in patients with the CB2-63 QQ variant than in those with the 63 QR (20%; P < .005) or RR variants (17.4%; P < .005). In logistic regression analysis, the CB2-63 QQ variant and fibrosis score were independent predictors of moderate or severe chronic hepatitis (HAI score, >8; P < .0001).
The CB2-63 QQ variant of CNR2 is associated with more severe inflammation and hepatocellular necrosis in patients with HCV infection.
大麻素受体 2（CB2）与肝病有关。大麻素受体 2 基因（CNR2）中的单核苷酸多态性 rs35761398 导致编码 CB2 的谷氨酸（Q）63 被精氨酸（R）取代，从而降低了基因产物的功能。我们研究了丙型肝炎病毒（HCV）感染患者中 CNR2 rs35761398 的影响。
我们研究了意大利南部 2 个肝脏单位的 169 例无症状慢性肝炎（抗 HCV 和 HCV RNA 阳性）连续患者。首先，在 2009 年 7 月至 2011 年 12 月收集肝活检样本。所有患者均未接受抗病毒治疗；通过聚合酶链反应分析确定 CNR2 基因型。
与 CB2-63 QR 或 RR 变体相比，携带 CB2-63 QQ 变体的患者血清转氨酶水平更高；他们的组织学活动指数（HAI）评分也更高（8.6 ± 3.8），而无 CB2-63 RR 变体的患者（5.3 ± 3.6；P <.005）或 CB2-63 QR 变体的患者（5.8 ± 3.3；P <.001）。不同 CNR2 变体的患者在纤维化阶段或脂肪变性评分上没有差异。携带 CB2-63 QQ 变体的患者更频繁地出现中度或重度慢性肝炎（HAI 评分> 8；55.5%），而携带 CB2-63 QR（20%；P <.005）或 RR 变体（17.4%；P <.005）的患者。在逻辑回归分析中，CB2-63 QQ 变体和纤维化评分是中度或重度慢性肝炎（HAI 评分> 8；P <.0001）的独立预测因子。
CNR2 的 CB2-63 QQ 变体与 HCV 感染患者更严重的炎症和肝细胞坏死有关。
