| Literature DB >> 25569262 |
R Herrero1, L M Real2, A Rivero-Juárez3, J A Pineda2, Á Camacho3, J Macías2, M Laplana4, P Konieczny1, F J Márquez1, J C Souto5, J M Soria5, I Saulle6, S Lo Caputo7, M Biasin6, A Rivero3, J Fibla4, A Caruz1.
Abstract
HIV-1 induces activation of complement through the classical and lectin pathways. However, the virus incorporates several membrane-bound or soluble regulators of complement activation (RCA) that inactivate complement. HIV-1 can also use the complement receptors (CRs) for complement-mediated antibody-dependent enhancement of infection (Ć-ADE). We hypothesize that hypofunctional polymorphisms in RCA or CRs may protect from HIV-1 infection. For this purpose, 139 SNPs located in 19 RCA and CRs genes were genotyped in a population of 201 Spanish HIV-1-exposed seronegative individuals (HESN) and 250 HIV-1-infected patients. Two SNPs were associated with infection susceptibility, rs1567190 in CR2 (odds ratio (OR) = 2.27, P = 1 × 10(-4)) and rs2842704 in C4BPA (OR = 2.11, P = 2 × 10(-4)). To replicate this finding, we analyzed a cohort of Italian, sexually HESN individuals. Although not significant (P = 0.25, OR = 1.57), similar genotypic proportions were obtained for the CR2 marker rs1567190. The results of the two association analyses were combined through a random effect meta-analysis, with a significant P-value of 2.6 x 10(-5) (OR = 2.07). Furthermore, we found that the protective CR2 genotype is correlated with lower levels CR2 mRNA as well as differences in the ratio of the long and short CR2 isoforms.Entities:
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Year: 2015 PMID： 25569262 DOI： 10.1038/gene.2014.71
Source DB: PubMed Journal: Genes Immun ISSN： 1466-4879 Impact factor: 2.676