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首页> 外文期刊>AIDS Research and Human Retroviruses >Influence of CCR5 and CCR2 genetic variants in the resistance/ susceptibility to HIV in serodiscordant couples from Colombia
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Influence of CCR5 and CCR2 genetic variants in the resistance/ susceptibility to HIV in serodiscordant couples from Colombia

机译：CCR5和CCR2遗传变异对哥伦比亚血清抗粘剂夫妇对HIV的抵抗/敏感性的影响

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The main genetic factor related to HIV-1 resistance is the CCR5-Δ32 mutation; however, the homozygous genotype is uncommon. The CCR5-Δ32 mutation along with single nucleotide polymorphisms (SNPs) in the CCR5 promoter and the CCR2-V64I mutation have been included in seven human haplogroups (HH) previously associated with resistance/susceptibility to HIV-1 infection and different rates of AIDS progression. Here, we determined the association of the CCR5 promoter SNPs, the CCR5-Δ32 mutation, CCR2-V64I SNP, and HH frequencies with resistance/susceptibility to HIV-1 infection in a cohort of HIV-1-serodiscordant couples from Colombia. Seventy HIV-1-exposed, but seronegative (HESN) individuals, 57 seropositives (SP), and 112 healthy controls (HC) were included. The CCR5-Δ32 mutation and CCR2-V64I SNP were identified by PCR, and the CCR5 promoter SNPs were evaluated by sequencing. None of the individuals exhibited a homozygous Δ32 genotype; the CCR2-I allele was more frequent in HESN (34%) than HC (23%) (p=0.039, OR=1.672). The frequency of the 29G allele was higher in SP than HC (p=0.003, OR=3). HHF2 showed a higher frequency in HC (19%) than SP (9%) (p=0.027), while HHG1 was more frequent in SP (11.1%) than in HC (4.2%) (p=0.019). The AGACCAC-CCR2-I-CCR5 wild-type haplotype showed a higher frequency in SP (14.2%) than in HC (3.7%) (p=0.001). In conclusion, the CCR5-Δ32 allele is not responsible for HIV-1 resistance in this HESN group; however, the CCR2-I allele could be protective, while the 29G allele might increase the likelihood of acquiring HIV-1 infection. HHG1 and the AGACCAC-CCR2-I-CCR5 wild-type haplotype might promote HIV-1 infection while HHF2 might be related to resistance. However, additional studies are required to evaluate the implications of these findings.
机译：与HIV-1耐药性相关的主要遗传因素是CCR5-Δ32突变。然而，纯合基因型并不常见。 CCR5启动子中的CCR5-Δ32突变以及单核苷酸多态性（SNP）和CCR2-V64I突变已包含在七个以前与HIV-1感染的耐药性/易感性以及不同的AIDS发病率相关的人类单倍体（HH）中。在这里，我们确定了来自哥伦比亚的一组HIV-1血清不一致的夫妇中CCR5启动子SNP，CCR5-Δ32突变，CCR2-V64I SNP和HH频率与对HIV-1感染的耐药性/敏感性的相关性。包括70名HIV-1暴露但血清阴性（HESN）的个体，57名血清阳性（SP）和112名健康对照（HC）。通过PCR鉴定CCR5-Δ32突变和CCR2-V64I SNP，并通过测序评估CCR5启动子SNP。没有一个个体表现出纯合的Δ32基因型。 HESN（34％）中的CCR2-I等位基因比HC（23％）更频繁（p = 0.039，OR = 1.672）。 SP中29G等位基因的频率高于HC（p = 0.003，OR = 3）。 HC（19％）中的HHF2频率高于SP（9％）（p = 0.027），而SP（11.1％）中HHG1的频率高于HC（4.2％）（p = 0.019）。 AGACCAC-CCR2-I-CCR5野生型单倍型在SP（14.2％）中的频率高于在HC（3.7％）中的频率（p = 0.001）。总之，CCR5-Δ32等位基因与该HESN组的HIV-1耐药性无关。然而，CCR2-I等位基因可能具有保护性，而29G等位基因可能会增加感染HIV-1的可能性。 HHG1和AGACCAC-CCR2-I-CCR5野生型单倍型可能会促进HIV-1感染，而HHF2可能与耐药性有关。但是，还需要其他研究来评估这些发现的含义。

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