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CCR5-Δ32对波兰人群中异性传播方式感染HIV的保护作用。

Protective effect of CCR5-Δ32 against HIV infection by the heterosexual mode of transmission in a Polish population.

作者信息

Zwolińska Katarzyna, Knysz Brygida, Rybka Katarzyna, Pazgan-Simon Monika, Gąsiorowski Jacek, Sobczyński Maciej, Gładysz Andrzej, Piasecki Egbert

机构信息

Laboratory of Virology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

出版信息

AIDS Res Hum Retroviruses. 2013 Jan;29(1):54-60. doi: 10.1089/AID.2011.0362. Epub 2012 Oct 9.

DOI:10.1089/AID.2011.0362
PMID:22957692
Abstract

Effects of chemokine receptor alleles (CCR5-Δ32 and CCR2-64I) on susceptibility to human immunodeficiency virus (HIV) infection were studied in a Polish population. The CCR5 and CCR2 genotypes were determined for 311 healthy, HIV-negative individuals (control group), 121 exposed to HIV infection but uninfected (EU group), and 470 HIV-positive patients. The frequency of the alleles in the control group was calculated as 0.12 for both CCR5-Δ32 and CCR2-64I. The logistic regression method was used to analyze the effects of the described factors. A protective effect was observed for the CCR5-Δ32 allele but only in the case of heterosexual exposure. Prevalence of the CCR5-Δ32/+ genotype in HIV(+) patients infected via the heterosexual route (n=61; 8.2%) was much lower than in the control group (n=311; 21.5%); in the heterosexually exposed uninfected group it was slightly higher (n=28; 25%). This suggested that in this mode of infection, the native CCR5 expression level was crucial for establishment of infection. Individuals with the CCR5-Δ32 allele have more than three times less chance of infection in the case of HIV heterosexual exposure (odds ratio, 3.37; 95% confidence interval, 1.055-10.76). However, a protective effect of the CCR5-Δ32/+ genotype was not observed in the case of intravenous drug users (IDUs). The rates of the genotype were similar in HIV-infected IDU individuals (n=356; 17.7%) and in exposed uninfected patients (n=84; 15.5%), not significantly different from control group. No effect of the CCR2 genotype was observed. The analysis revealed that the important factor increasing infection risk was, in particular, hepatitis C virus (HCV) infection (odds ratio, 12.9). Moreover, the effect of HCV infection was found to be age dependent. Susceptibility to HIV infection resulting from HCV positivity became weaker (6% per year) with increasing age.

摘要

在波兰人群中研究了趋化因子受体等位基因(CCR5-Δ32和CCR2-64I)对人类免疫缺陷病毒(HIV)感染易感性的影响。确定了311名健康的HIV阴性个体(对照组)、121名暴露于HIV感染但未感染的个体(暴露未感染组)和470名HIV阳性患者的CCR5和CCR2基因型。CCR5-Δ32和CCR2-64I在对照组中的等位基因频率均计算为0.12。采用逻辑回归方法分析上述因素的影响。观察到CCR5-Δ32等位基因具有保护作用,但仅在异性接触的情况下。通过异性途径感染的HIV(+)患者中CCR5-Δ32/+基因型的患病率(n=61;8.2%)远低于对照组(n=311;21.5%);在异性接触未感染组中略高(n=28;25%)。这表明在这种感染方式中,天然CCR5表达水平对于感染的建立至关重要。在HIV异性接触的情况下,携带CCR5-Δ32等位基因的个体感染几率降低三倍多(优势比,3.37;95%置信区间,1.055-10.76)。然而,在静脉吸毒者(IDU)中未观察到CCR-Δ32/+基因型的保护作用。HIV感染的IDU个体(n=356;17.7%)和暴露未感染患者(n=84;15.5%)中该基因型的比例相似,与对照组无显著差异。未观察到CCR2基因型的影响。分析表明,增加感染风险的重要因素尤其是丙型肝炎病毒(HCV)感染(优势比,12.9)。此外,发现HCV感染的影响与年龄有关。随着年龄增长,HCV阳性导致的HIV感染易感性逐渐减弱(每年6%)。

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