Differential prevalence of the HLA-C-35 CC genotype among viremic long term non-progressor and elite controller HIV plus individuals
Differential prevalence of the HLA-C-35 CC genotype among viremic long term non-progressor and elite controller HIV plus individuals
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DOI：
10.1016/j.imbio.2011.12.012
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发表时间：
2012-09-01
期刊：
影响因子：
2.8
通讯作者：
Este, Jose A.
中科院分区：
文献类型：
--
作者：
Ballana, Ester;Ruiz-de Andres, Alba;Este, Jose A.
对HIV感染的易感性和疾病进展是受环境和遗传因素调节的复杂特征，影响先天和适应性免疫应答以及其他细胞过程。HLA-C基因座上游35 kb的单核苷酸多态性（SNP）（-35 C/T）先前已被证明与HLA-C表达增加和HIV-1控制改善相关。在这里，我们对639名受试者（180名未感染患者，304名HIV进展者和155名LTNP）进行了-35C/T SNP基因分型，并证实了-35C/T变异与LTNP表型的相关性。普通人群受试者的基因型频率与HIV进展者的基因型频率无显著差异（p值= 0.472）。然而，当LTNP与单独的HIV进展者（p值< 0.0001）或进展者和未感染受试者一起（p值< 0.0001）比较时，鉴定出保护性CC基因型的显著更高频率。当考虑单独的病毒血症LTNP（精英控制者;病毒载量低于50拷贝/ml）时，与HIV进展者相比，-35 CC基因型并没有过多。相反，发现与病毒血症LTNP组（病毒载量低于10.000拷贝/ml）有显著相关性。这些结果表明，其他因素单独或结合-35 CC基因型可能发挥重要作用，在区分精英控制者状态从LTNP。不同遗传变异的组合可能具有决定HIV感染过程的累加或上位效应。(C)2012 Elsevier GmbH. All rights reserved.
Susceptibility to HIV infection and disease progression are complex traits modulated by environmental and genetic factors, affecting innate and adaptive immune responses, among other cellular processes. A single nucleotide polymorphism (SNP) 35 kb upstream of the HLA-C gene locus (-35C/T) was previously shown to correlate with increased HLA-C expression and improved control of HIV-1. Here, we genotyped the -35C/T SNP in 639 subjects (180 uninfected patients, 304 HIV progressors and 155 LTNP) and confirmed the association of the -35C/T variant with the LTNP phenotype. The genotype frequencies in the general population subjects did not differ significantly from those seen in HIV progressors (p-value = 0.472). However, a significant higher frequency of the protective CC genotype was identified when LTNP were compared either with HIV progressors alone (p-value < 0.0001) or progressors and uninfected subjects together (p-value < 0.0001). When considering aviremic LTNP alone (elite controllers; viral load below 50 copies/ml), the -35 CC genotype was not overrepresented compared to HIV progressors. Conversely, a significant association was found with the viremic LTNP groups (viral loads below 10.000 copies/ml). These results suggest that other factors alone or in combination with the -35 CC genotype may play an important role in differentiating the elite controller status from LTNP. Combination of different genetic variants may have additive or epistatic effects determining the HIV course of infection. (C) 2012 Elsevier GmbH. All rights reserved.