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CCR5Δ32 突变在保护曼氏血吸虫感染患者免受丙型肝炎病毒感染或进展中的作用。

Role of CCR5Δ32 mutation in protecting patients with Schistosoma mansoni infection against hepatitis C viral infection or progression.

机构信息

Department of Parasitology, Faculty of Medicine, Suez Canal University, 4.5 Km region, Ismailia 41522, Egypt.

出版信息

Parasitol Res. 2013 Jul;112(7):2745-52. doi: 10.1007/s00436-013-3380-9. Epub 2013 Mar 21.

Abstract

Schistosomiasis has been incriminated in the significant increase in hepatitis C virus (HCV) infections, although the association has not been adequately explained. We hypothesized that the CCR5Δ32 mutation may be involved in the high prevalence of HCV with schistosomiasis. The aim was to explore the association between the CCR5Δ32 mutation in schistosomiasis patients and protection against HCV infection or progression. We compared 220 schistosomiasis patients (S group) and 190 patients with HCV and schistosomiasis (HCV/S group) for the presence of the CCR5Δ32 mutation. Clinical, biochemical, and radiological assessments were done. HCV infection was diagnosed with anti-HCV antibodies and a recombinant HCV antigen-based rapid immunochromatographic test, and confirmed by HCV reverse transcriptase PCR. HCV genotyping was done by reverse hybridization line probe assay. Schistosomiasis was diagnosed by FAST-ELISA and indirect hemagglutination for Schistosoma mansoni antibodies, and stool analysis for ova. Polymorphisms of the CCR5 receptor gene were assessed by PCR-based genotyping of the 32-bp deletion at the CCR5 locus in whole blood. Of HCV/S patients, 91.6 vs. 91.8 % of S patients had CCR5 WT/WT homozygosity (nonmutants). Heterozygous and homozygous CCR5Δ32 mutation patterns (CCR5Δ32/WT and CCR5Δ32/Δ32) were distributed similarly in the HCV/S and S groups (6.8 vs. 7.2 % and 0.53 vs. 0.90 %, respectively; p > 0.05, OR = 0.97). Genotype 4 was the predominant viral genotype (93 % of cases). No differences were observed in CCR5 gene patterns according to viral genotype, viral RNA count, or ALT level. However, CCR5Δ32 mutants (homozygous and heterozygous) had a lower rate of severe hepatic fibrosis vs. nonmutants (27 vs. 42 %, p = 0.101, OR = 0.51). Moreover, 53.4 % of CCR5Δ32/WT mutants showed spontaneous viral clearance vs. 26.2 % of nonmutants (p = 0.000, OR = 4.1). In conclusion, no association was detected between the CCR5Δ32 mutation and HCV disease susceptibility in schistosomiasis patients. However, patients with the CCR5Δ32 mutation and HCV infection were less prone to severe hepatic fibrosis and more likely to have spontaneous viral clearance than patients with the nonmutant genotype.

摘要

血吸虫病被认为是丙型肝炎病毒(HCV)感染显著增加的原因,尽管这种关联尚未得到充分解释。我们假设 CCR5Δ32 突变可能与血吸虫病中的 HCV 高患病率有关。目的是探讨血吸虫病患者 CCR5Δ32 突变与 HCV 感染或进展的保护作用之间的关系。我们比较了 220 例血吸虫病患者(S 组)和 190 例 HCV 和血吸虫病患者(HCV/S 组)中 CCR5Δ32 突变的存在情况。进行了临床、生化和影像学评估。通过抗 HCV 抗体和基于 HCV 重组抗原的快速免疫层析检测诊断 HCV 感染,并通过 HCV 逆转录酶 PCR 确认。通过反向杂交线探针分析进行 HCV 基因分型。通过快速 ELISA 和间接血凝法检测曼氏血吸虫抗体以及粪便虫卵分析诊断血吸虫病。通过对全血 CCR5 基因座的 32 个碱基对缺失进行基于 PCR 的基因分型,评估 CCR5 受体基因的多态性。在 HCV/S 患者中,91.6%与 S 患者的 CCR5 WT/WT 纯合子(非突变体)相同。杂合和纯合 CCR5Δ32 突变模式(CCR5Δ32/WT 和 CCR5Δ32/Δ32)在 HCV/S 和 S 组中的分布相似(分别为 6.8%和 7.2%和 0.53%和 0.90%;p>0.05,OR=0.97)。基因型 4 是主要的病毒基因型(93%的病例)。根据病毒基因型、病毒 RNA 计数或 ALT 水平,CCR5 基因模式没有差异。然而,与非突变体相比,CCR5Δ32 突变体(纯合子和杂合子)的严重肝纤维化发生率较低(27%与 42%,p=0.101,OR=0.51)。此外,53.4%的 CCR5Δ32/WT 突变体与 26.2%的非突变体相比自发清除病毒(p=0.000,OR=4.1)。总之,在血吸虫病患者中,未发现 CCR5Δ32 突变与 HCV 疾病易感性之间存在关联。然而,与非突变基因型患者相比,携带 CCR5Δ32 突变和 HCV 感染的患者更不易发生严重肝纤维化,更可能自发清除病毒。

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