汉族人群中 CCL3 和 CCL4 多态性与 HCV 清除的关联。

The association of CCL3 and CCL4 polymorphisms with HCV clearance in Chinese Han population.

机构信息

Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

Department of Infectious Diseases, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

出版信息

Gene. 2018 Jul 30;665:35-40. doi: 10.1016/j.gene.2018.04.079. Epub 2018 Apr 27.

DOI:10.1016/j.gene.2018.04.079

PMID:29705123

Abstract

AIM

To explore the association of CCL3 (rs1063340) and CCL4 (rs1049807) polymorphisms with hepatitis C virus (HCV) clearance and sustained virologic response (SVR).

METHODS

Two populations were enrolled in the current study; one was a general population including 1585 untreated individuals, with HCV infection and the other was a treatment population comprising 353 HCV-infected patients treated with pegylated interferon-α and ribavirin (pegIFN-α/RBV). Two single nucleotide polymorphisms (SNPs) were genotyped, and the relationship between HCV clearance and treatment outcome was analysed.

RESULTS

The general population comprised 995 persistent HCV cases (both HCV RNA and anti-HCV were positive) and 590 spontaneous clearance cases (HCV RNA was negative, but anti-HCV was positive). An association between the SNPs and HCV clearance was not found in our study. The treatment population consisted of 235 patients who achieved SVR and 118 non-responders. Variants of both SNPs (rs1063340-C and rs1049807-G) were associated with a reduction in SVR following IFN treatment (dominant model: P = 0.026 for rs1063340 and P = 0.048 for rs1049807). In addition, the ancestral alleles of rs1063340 and rs1049807 increased the likelihood of virus clearance by 62% compared to both the derived and minor alleles of the two SNPs (P = 0.040).The interaction analysis showed that the level of glucose interacted with the association of rs1063340 and SVR.

CONCLUSIONS

Our results suggested that genetic variants at the CCL3 and CCL4 loci may be marker SNPs for risk of HCV treatment outcome.

摘要

目的

探讨 CCL3（rs1063340）和 CCL4（rs1049807）多态性与丙型肝炎病毒（HCV）清除和持续病毒学应答（SVR）的关系。

方法

本研究纳入了两个人群；一个是包括 1585 名未经治疗的 HCV 感染个体的一般人群，另一个是接受聚乙二醇干扰素-α和利巴韦林（pegIFN-α/RBV）治疗的 353 例 HCV 感染患者的治疗人群。对两个单核苷酸多态性（SNP）进行基因分型，并分析 HCV 清除与治疗结果之间的关系。

结果

一般人群包括 995 例持续性 HCV 病例（HCV RNA 和抗-HCV 均为阳性）和 590 例自发清除病例（HCV RNA 为阴性，但抗-HCV 为阳性）。本研究未发现 SNP 与 HCV 清除之间存在关联。治疗人群包括 235 例达到 SVR 的患者和 118 例无应答者。两个 SNP（rs1063340-C 和 rs1049807-G）的变体与 IFN 治疗后的 SVR 降低相关（显性模型：rs1063340 为 P=0.026，rs1049807 为 P=0.048）。此外，与两个 SNP 的衍生和次要等位基因相比，rs1063340 和 rs1049807 的原始等位基因使病毒清除的可能性增加了 62%（P=0.040）。交互分析显示，葡萄糖水平与 rs1063340 与 SVR 的关联存在交互作用。