Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan.
Core Research Facilities for Basic Science, Research Center for Medical Sciences, Jikei University School of Medicine, Tokyo, Japan.
J Med Virol. 2015 Nov;87(11):1904-12. doi: 10.1002/jmv.24244. Epub 2015 May 11.
Although several vitamin D-related gene polymorphisms were reported to affect the outcome of pegylated interferon/ribavirin (PR) therapy in chronic hepatitis C patients, there are no reports on the impact of the vitamin D-related gene polymorphisms in PR therapy combined with protease inhibitor (PI). Vitamin D-related gene polymorphisms were determined in 177 genotype 1b-infected chronic hepatitis C patients who received 12 weeks of PR therapy with telaprevir, a first-generation PI, followed by 12 weeks of PR therapy. The sustained virologic response (SVR) rate was 83.1% (147 of 177 patients). The frequencies of vitamin D-related gene polymorphisms were: 83 non-TT and 94 TT genotypes for GC, 97 non-AA and 80 AA genotypes for DHCR7, 151 non-AA and 26 AA genotypes for CYP2R1, 162 non-GG and 15 GG genotypes for CYP27B1, and 105 non-GG and 72 GG genotypes for VDR gene. Multivariate analysis extracted IL28B TT genotype (P = 2.05 × 10(-6)) and serum 25(OH) D3 level (P = 0.024) as independent factors contributing to the achieving of SVR. The SVR rate in IL28B TT genotype patients with serum 25(OH) D3 level of < 25 ng/ml was significantly low compared to other patients. None of the vitamin D-related gene polymorphisms affected the treatment outcome and serum 25(OH) D3 level. In conclusions, the IL28B polymorphism and serum 25(OH) D3 level contributed significantly and independently to SVR in PR combined with PI for genotype 1b-infected chronic hepatitis C patients. However, none of vitamin D-related gene polymorphisms had an impact on the treatment outcome and serum 25(OH) D3 level.
尽管有几项与维生素 D 相关的基因多态性被报道会影响聚乙二醇干扰素/利巴韦林 (PR) 治疗慢性丙型肝炎患者的疗效，但尚无关于 PR 联合蛋白酶抑制剂 (PI) 治疗中维生素 D 相关基因多态性影响的报告。在接受第一代 PI 特拉匹韦联合 PR 治疗 12 周，随后再接受 PR 治疗 12 周的 177 例基因型 1b 感染慢性丙型肝炎患者中，确定了维生素 D 相关基因多态性。持续病毒学应答 (SVR) 率为 83.1%（177 例患者中的 147 例）。维生素 D 相关基因多态性的频率为：GC 中的 83 个非 TT 和 94 个 TT 基因型，DHCR7 中的 97 个非 AA 和 80 个 AA 基因型，CYP2R1 中的 151 个非 AA 和 26 个 AA 基因型，CYP27B1 中的 162 个非 GG 和 15 个 GG 基因型，VDR 基因中的 105 个非 GG 和 72 个 GG 基因型。多变量分析提取 IL28B TT 基因型（P=2.05×10(-6))和血清 25(OH)D3 水平（P=0.024)是达到 SVR 的独立因素。与其他患者相比，IL28B TT 基因型患者血清 25(OH)D3 水平<25ng/ml 的 SVR 率显著降低。维生素 D 相关基因多态性均不影响治疗效果和血清 25(OH)D3 水平。总之，IL28B 多态性和血清 25(OH)D3 水平对基因型 1b 感染慢性丙型肝炎患者 PR 联合 PI 治疗的 SVR 有显著的独立影响。然而，维生素 D 相关基因多态性对治疗效果和血清 25(OH)D3 水平均无影响。
