Association of complement receptor 2 polymorphisms with innate resistance to HIV-1 infection.
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| 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.
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| Authors | R Herrero, L M Real, A Rivero-Juárez, J A Pineda, Á Camacho, J Macías, M Laplana, P Konieczny, F J Márquez, J C Souto, J M Soria, I Saulle, S Lo Caputo, M Biasin, A Rivero, J Fibla, A Caruz |
| Journal | Genes and immunity (Genes Immun) Vol. 16 Issue 2 Pg. 134-41 (Mar 2015) ISSN: 1476-5470 [Electronic] England |
| PMID | 25569262 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't) |
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