Li Hui, Liu Ting-Jun, Hong Ze-Hui
Department of Genetics and Developmental Biology, Southeast University School of Medicine, Nanjing 210009, China; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University, Nanjing 210096, China.
Institute of Life Sciences, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
Infect Genet Evol. 2014 Jun;24:99-104. doi: 10.1016/j.meegid.2014.03.009. Epub 2014 Mar 18.
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 (CCR5Δ32, CCR5 m303, CCR5 59029A/G, CCR2 64I, RANTES -403A/G, RANTES -28C/G and SDF1 3'-A) were screened. CCR5Δ32 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.
趋化因子和趋化因子受体对HIV-1感染中的免疫反应至关重要。尽管已经开展了许多研究来调查趋化因子和趋化因子受体基因多态性与宿主对HIV-1感染易感性之间的关系，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例HIV-1血清阳性患者、388例年龄匹配的健康对照以及49例静脉吸毒者（IDU）中HIV-1暴露血清阴性个体（HESN），以确定宿主遗传因素对HIV-1感染的影响。对四个已知趋化因子/趋化因子受体基因（CCR5Δ32、CCR5 m303、CCR5 59029A/G、CCR2 64I、RANTES -403A/G、RANTES -28C/G和SDF1 3'-A）上的七个多态性进行了筛查。CCR5Δ32和CCR5 m303在中国汉族人群中不存在或罕见，这可能不是宿主对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。RANTES -403A等位基因在HIV-1患者中的频率显著低于健康献血者（p = 0.0005）和HESN组（p = 0.035），这意味着A等位基因与降低的HIV-1感染风险相关。评估了不同的遗传模型以研究这种关联（AA与GG + AG相比，OR = 0.38，95% CI，0.22 - 0.65，p = 0.0004；A与G相比，OR = 0.66，95% CI，0.52 - 0.84，p = 0.0006），这也支持了这种关联。HIV-1患者与健康对照之间（基因型分布：p = 0.072；等位基因分布：p = 0.027）或HIV-1血清阴性组之间（基因型分布：p = 0.036；等位基因分布：p = 0.383）RANTES -28的基因型和等位基因分布均处于边缘显著水平，经Bonferroni校正后未观察到显著差异。所有这些结果表明RANTES -403A可能与降低的HIV-1感染易感性相关，而RANTES -28位点则不然。由于缺乏患者的临床信息，本研究无法评估这些多态性是否影响艾滋病疾病进展及其在不同HIV-1感染途径中的作用，需要在正在进行的研究中进行评估。
