Gene polymorphisms in CCR5, CCR2, SDF1 and RANTES among Chinese Han population with HIV-1 infection
Gene polymorphisms in CCR5, CCR2, SDF1 and RANTES among Chinese Han population with HIV-1 infection
复制标题
DOI：
10.1016/j.meegid.2014.03.009
复制
发表时间：
2014-06-01
影响因子：
3.2
通讯作者：
Hong, Ze-Hui
中科院分区：
文献类型：
--
作者：
Li, Hui;Liu, Ting-Jun;Hong, Ze-Hui
趋化因子和趋化因子受体对于 HIV-1 感染的免疫反应至关重要。尽管已经进行了许多研究来探讨趋化因子和趋化因子受体基因多态性与宿主对HIV-1感染的易感性之间的关系，但结论仍存在争议。在本研究中，纳入了来自中国汉族人群的 287 名 HIV-1 血清阳性患者、388 名种族年龄匹配的健康对照者和 49 名静脉注射吸毒者 (IDU) HIV-1 暴露血清阴性个体 (HESN) 的队列，以确定宿主遗传因素对 HIV-1 感染的影响。筛选了四种已知趋化因子/趋化因子受体基因（CCR5 Delta 32、CCR5 m303、CCR5 59029A/G、CCR2 64I、RANTES -403A/G、RANTES -28C/G 和 SDF1 3 '-A）的七个多态性。 CCR5D32和CCR5 m303在中国汉族人群中缺失或少见，这可能不是宿主HIV-1感染的遗传保护因素。我们的结果显示CCR5 59029A/G、CCR2 64I和SDF1 3'-A与宿主对HIV-1感染的抵抗力无关。 HIV-1 患者中 RANTES -403A 等位基因的频率显着低于健康献血者 (p = 0.0005) 和 HESN 组 (p = 0.035)，这表明 A 等位基因与降低 HIV-1 感染风险之间存在关联。我们评估了不同的遗传模型来研究这种关联（AA vs. GG + AG，OR = 0.38 95% CI，0.22-0.65 p = 0.0004；A vs. G，OR = 0.66 95% CI，0.52-0.84 p = 0.0006），也支持了这种关联。 HIV-1患者和健康对照（基因型谱：p = 0.072；等位基因谱：p = 0.027）或HIV-1血清阴性组（基因型谱：p = 0.036；等位基因谱：p = 0.383）之间RANTES -28的基因型和等位基因分布均处于显着性边缘水平，这在Bonferroni校正后未观察到。所有这些结果表明 RANTES -403A 可能与 HIV-1 感染易感性降低相关，而 RANTES -28 位点则不然。由于缺乏患者的临床信息，这些多态性是否影响艾滋病疾病进展以及它们在不同HIV-1感染途径中的作用无法在目前的研究中进行，需要在正在进行的研究中进行评估。 (C) 2014 Elsevier B.V. 保留所有权利。
Chemokines and chemokine receptors are crucial for immune response in HIV-1 infection. Although many studies have been done to investigate the relationship between chemokines and chemokine receptor gene polymorphisms and host's susceptibility to HIV-1 infection, the conclusions are under debate. In the present study, a cohort of 287 HIV-1 seropositive patients, 388 ethnically age-matched healthy controls and 49 intravenous drug users (IDUs) HIV-1 exposed seronegative individuals (HESN) from Chinese Han population were enrolled in order to determine the influence of host genetic factors on HIV-1 infection. Seven polymorphisms on four known chemokines/chemokine receptor genes (CCR5 Delta 32, CCR5 m303, CCR5 59029A/G, CCR2 64I, RANTES -403A/G, RANTES -28C/G and SDF1 3 '-A) were screened. CCR5D32 and CCR5 m303 were absent or infrequent in Chinese Han population, which may not be hosts' genetic protective factors for HIV-1 infection. Our results showed the CCR5 59029A/G, CCR2 64I and SDF1 3 '-A were not associated with host's resistance to HIV-1 infection. The frequency of RANTES -403A allele was significantly lower in HIV-1 patients than in healthy blood donors (p = 0.0005) and HESN group (p = 0.035), which implied the association between A allele and reduced HIV-1 infection risk. Different genetic models were assessed to investigate this association (AA vs. GG + AG, OR = 0.38 95% CI, 0.22-0.65 p = 0.0004; A vs. G, OR = 0.66 95% CI, 0.52-0.84 p = 0.0006), which supported this association, either. The genotype and allele distribution of RANTES -28 between HIV-1 patients and healthy controls (genotype profile: p = 0.072; allele profile: p = 0.027) or HIV-1 seronegative group (genotype profile: p = 0.036; allele profile: p = 0.383) were both at the marginal level of significance, which were not observed after Bonferroni correction. All these results suggest the RANTES -403A may be associated with reduced susceptibility to HIV-1 infection, while the RANTES -28 locus not. By lack of the patients' clinical information, whether these polymorphisms affect AIDS disease progression and their role in different HIV-1 infection routes could not performed in present study and needs to be assessed in ongoing studies. (C) 2014 Elsevier B.V. All rights reserved.