Department of Microbiology, Faculty of Medicine, University of Tartu, Tartu, Estonia.
PLoS One. 2013 Jul 25;8(7):e70561. doi: 10.1371/journal.pone.0070561. Print 2013.
Up to 90% HIV-1 positive intravenous drug users (IDUs) are co-infected with HCV. Although best recognized for its function as a major co-receptor for cell entry of HIV, CC chemokine receptor 5 (CCR5) has also been implicated in the pathogenesis of HCV infection. Here, we investigated whether CCR5 haplotypes influence HIV-1 and HCV seropositivity among 373 Caucasian IDUs from Estonia.
Of these IDUs, 56% and 44% were HIV and HCV seropositive, respectively, and 47% were coinfected. 500 blood donors seronegative for HIV and HCV were also evaluated. CCR5 haplotypes (HHA to HHG*2) were derived after genotyping nine CCR2-CCR5 polymorphisms. The association between CCR5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Co-variates included in the models were length of intravenous drug use, HBV serostatus and copy number of CCL3L1, the gene encoding the most potent HIV-suppressive chemokine and ligand for CCR5.
Compared to IDUs seronegative for both HCV and HIV (HCV-/HIV-), IDUs who were HCV+/HIV- and HCV+/HIV+were 92% and 82%, respectively, less likely to possess the CCR5-HHG1 haplotype, after controlling for co-variates (P(adjusted) = 1.89 × 10(-4) and 0.003, respectively). This association was mostly due to subjects bearing the CCR5 HHE and HHG1 haplotype pairs. Approximately 25% and<10% of HCV-/HIV- IDUs and HCV-/HIV- blood donors, respectively, possessed the HHE/HHG*1 genotype.
Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs.
多达 90%的 HIV-1 阳性静脉吸毒者（IDU）同时感染 HCV。虽然趋化因子受体 5（CCR5）最被认为是 HIV 进入细胞的主要辅助受体之一，但它也与 HCV 感染的发病机制有关。在这里，我们研究了 Estonian 的 373 名高加索 IDU 中 CCR5 单倍型是否影响 HIV-1 和 HCV 血清阳性率。
这些 IDU 中，56%和 44%分别为 HIV 和 HCV 血清阳性，47%为合并感染。还评估了 500 名 HIV 和 HCV 血清阴性的献血者。CCR5 单倍型（HHA 至 HHG*2）是在对 9 个 CCR2-CCR5 多态性进行基因分型后得出的。使用逻辑回归分析确定 CCR5 单倍型与 HIV 和/或 HCV 血清阳性之间的关联。纳入模型的协变量包括静脉吸毒时间、HBV 血清状态和 CCL3L1 的拷贝数，CCL3L1 是编码最强 HIV 抑制性趋化因子和 CCR5 配体的基因。
与 HCV 和 HIV 均为阴性的 IDU（HCV-/HIV-）相比，HCV+/HIV-和 HCV+/HIV+的 IDU 分别不太可能携带 CCR5-HHG1 单倍型，在控制了协变量后（P（调整）= 1.89×10(-4) 和 0.003）。这种关联主要是由于携带 CCR5 HHE 和 HHG1 单倍型对的受试者。大约 25%和<10%的 HCV-/HIV- IDU 和 HCV-/HIV- 献血者分别携带 HHE/HHG*1 基因型。
我们的研究结果表明，携带 HHG*1 的 CCR5 基因型影响一组高加索 IDU 的 HCV 血清阳性率。
