维生素D相关基因多态性可预测泰国慢性丙型肝炎患者对聚乙二醇干扰素治疗的反应。

Vitamin D-related gene polymorphism predict treatment response to pegylated interferon-based therapy in Thai chronic hepatitis C patients.

作者信息

Thanapirom Kessarin, Suksawatamnuay Sirinporn, Sukeepaisarnjaroen Wattana, Tangkijvanich Pisit, Treeprasertsuk Sombat, Thaimai Panarat, Wasitthankasem Rujipat, Poovorawan Yong, Komolmit Piyawat

机构信息

Divisions of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Pathumwan District, Bangkok, 10330, Thailand.

Center of Excellence in Liver Diseases, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, No. 1873 Rama IV road, Bangkok, 10330, Thailand.

出版信息

BMC Gastroenterol. 2017 Apr 17;17(1):54. doi: 10.1186/s12876-017-0613-x.

DOI:10.1186/s12876-017-0613-x

PMID:28415985

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5392932/

Abstract

BACKGROUND

Patients with chronic hepatitis C (HCV) infection have high prevalence of vitamin D deficiency. Genome-wide association study data has showed that several genetic variants within vitamin D cascade affect vitamin D function. This study aimed to determine whether genetic polymorphisms of genes in the vitamin D pathway are associated with treatment responses to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection.

METHODS

The study included 623 Thai patients from 2 university hospitals diagnosed with chronic HCV infection who were treated with a PEG-IFN and ribavirin. Patients were genotyped for functional variants on vitamin D synthetic pathway including GC (rs4588, rs7041, rs22020, rs2282679), CYP2R1 (rs2060793, rs12794714), CYP27B1 (rs10877012), and DHCR7 (rs12785878). Pre-treatment predictors of sustained virologic response (SVR) at 24 weeks following discontinuation of therapy were identified using a logistic regression analysis.

RESULTS

SVR was achieved by 60.5% of patients (52.9% with HCV genotype 1; 66.7% with HCV non-genotype 1). In 44.6% of HCV genotype 1-infected patients, only the variant rs12785878 in the DHCR7 locus was significantly associated with an SVR. HCV genotype 1 patients who had DHCR7 rs12785878 GT/TT had a higher rate of SVR than those with the GG allele (59.7% vs. 43.4%, P = 0.03), but in HCV non-genotype 1-infected patients, the SVR rate did not differ between the two groups (63.3% and 59.1% for GT/TT and GG allele, P = 0.54). By multivariate analysis, liver fibrosis stage 0-1 (OR = 5.00; 95% CI, 2.02-12.37; P < 0.001), and DHCR7 rs12785878 GT/TT allele (OR = 2.69; 95% CI, 1.03-7.05; P = 0.04) were independent pre-treatment predictors of SVR following PEG-IFN-based therapy in HCV genotype 1 patients. Baseline HCV RNA < 400,000 IU/ml (OR = 1.96; 95% CI, 1.13-3.39; P = 0.02) was the only independent predictor of SVR in HCV non-genotype 1 patients. The polymorphisms of GC, CYP2R1 and CYP27B1 were not associated with treatment outcome even in genotype 1 or non-genotype 1 HCV infection.

CONCLUSION

The DHCR7 polymorphism may be a pre-treatment predictive marker for response to PEG-IFN-based therapy in chronic HCV genotype 1 infection.

摘要

背景

慢性丙型肝炎（HCV）感染患者维生素D缺乏的患病率很高。全基因组关联研究数据表明，维生素D级联反应中的几个基因变异会影响维生素D功能。本研究旨在确定维生素D途径中基因的遗传多态性是否与慢性HCV感染患者基于聚乙二醇干扰素（PEG-IFN）治疗的反应相关。

方法

该研究纳入了来自2所大学医院的623例被诊断为慢性HCV感染且接受PEG-IFN和利巴韦林治疗的泰国患者。对患者进行维生素D合成途径功能变异的基因分型，包括GC（rs4588、rs7041、rs22020、rs2282679）、CYP2R1（rs2060793、rs12794714）、CYP27B1（rs10877012）和DHCR7（rs12785878）。使用逻辑回归分析确定治疗停药后24周持续病毒学应答（SVR）的治疗前预测指标。

结果

60.5%的患者实现了SVR（HCV基因1型患者为52.9%；非HCV基因1型患者为66.7%）。在44.6%的HCV基因1型感染患者中，仅DHCR7基因座中的rs12785878变异与SVR显著相关。携带DHCR7 rs12785878 GT/TT的HCV基因1型患者的SVR率高于携带GG等位基因的患者（59.7%对43.4%，P = 0.03），但在非HCV基因1型感染患者中，两组的SVR率无差异（GT/TT和GG等位基因分别为63.3%和59.1%，P = 0.54）。通过多变量分析，肝纤维化0 - 1期（OR = 5.00；95%CI，2.02 - 12.37；P < 0.001）和DHCR7 rs12785878 GT/TT等位基因（OR = 2.69；95%CI，1.03 - 7.05；P = 0.04）是HCV基因1型患者基于PEG-IFN治疗后SVR的独立治疗前预测指标。基线HCV RNA < 400,000 IU/ml（OR = 1.96；95%CI，1.13 - 3.39；P = 0.02）是非HCV基因1型患者SVR的唯一独立预测指标。即使在基因1型或非基因1型HCV感染中，GC、CYP2R1和CYP27B1的多态性也与治疗结果无关。