The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients
The vitamin D receptor gene bAt (CCA) haplotype impairs the response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C patients
复制标题
DOI：
10.3851/imp2018
复制
发表时间：
2012-01-01
影响因子：
1.2
通讯作者：
Geier, Andreas
中科院分区：
文献类型：
--
作者：
Baur, Katharina;Mertens, Joachim C.;Geier, Andreas
背景：慢性丙型肝炎感染是终末期肝病的主要原因。治疗结果受25-OH维生素D缺乏症的影响。为了进一步解决这一问题，我们的研究调查的影响，维生素D受体（NR 1 I1）的单体型和血浆维生素D水平的综合影响，在一个良好的描述队列丙型肝炎patients.Methods：共招募了155名慢性丙型肝炎患者从瑞士丙型肝炎队列研究NR 1 I1基因分型和血浆25-OH维生素D水平的测量。NR 1 I1基因型数据和血浆25-OH维生素D水平的联合效应进行了分析治疗反应（持续病毒学应答）。结果：观察到治疗无应答与NR 1 I1 CCA（bAt）单倍型之间存在强相关性，该单倍型由rs 1544410（BsmI）C、rs7975232（ApaI）C和rs731236（TaqI）A等位基因组成。在携带CCA单倍型的HCV患者中，50.3%为无应答者（比值比[ OR] 1.69，95%CI 1.07，2.67; P=0.028）。在CCCCAA基因型组合中观察到类似的相关性（OR 2.94，95%CI 1.36，6.37; P=0.007）。多因素分析证实CCCCAA基因型是无应答的独立危险因素（OR 2.50，95%CI 1.07，5.87; P=0.034）。分析联合效应，低25-OH维生素D水平对持续病毒学应答的显著影响仅见于NR 1 I1 CCA（bAt）单倍型不利的患者（非SVR的OR为3.55; 95% CI为1.005，12.57; P=0.049）。NR 1 I1维生素D受体多态性影响对聚乙二醇干扰素/利巴韦林的应答-基于治疗慢性丙型肝炎，并发挥加性遗传易感性，以先前描述的低25-OH维生素D血清水平。
Background: Chronic hepatitis C infection is a major cause of end-stage liver disease. Therapy outcome is influenced by 25-OH vitamin D deficiency. To further address this observation, our study investigates the impact of the vitamin D receptor (NR1I1) haplotype and combined effects of plasma vitamin D levels in a well-described cohort of hepatitis C patients.Methods: A total of 155 chronic hepatitis C patients were recruited from the Swiss Hepatitis C Cohort Study for NR1I1 genotyping and plasma 25-OH vitamin D level measurement. NR1I1 genotype data and combined effects of plasma 25-OH vitamin D level were analysed regarding therapy response (sustained virological response).Results: A strong association was observed between therapy non-response and the NR1I1 CCA (bAt) haplotype consisting of rs1544410 (BsmI) C, rs7975232 (ApaI) C and rs731236 (TaqI) A alleles. Of the HCV patients carrying the CCA haplotype, 50.3% were non-responders (odds ratio [ OR] 1.69, 95% CI 1.07, 2.67; P=0.028). A similar association was observed for the combinational CCCCAA genotype (OR 2.94, 95% CI 1.36, 6.37; P=0.007). The combinational CCCCAA genotype was confirmed as an independent risk factor for non-response in multi-variate analysis (OR 2.50, 95% CI 1.07, 5.87; P=0.034). Analysing combined effects, a significant impact of low 25-OH vitamin D levels on sustained virological response were only seen in patients with the unfavourable NR1I1 CCA (bAt) haplotype (OR for non-SVR 3.55; 95% CI 1.005, 12.57; P=0.049).Conclusions: NR1I1 vitamin D receptor polymorphisms influence response to pegylated-interferon/ribavirin-based therapy in chronic hepatitis C and exert an additive genetic predisposition to previously described low 25-OH vitamin D serum levels.