Association of complement receptor 2 polymorphisms withinnate resistance to HIV-1 infection

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Issue date
2015-03
Author
Herrero, Rocío
Real, Luis M.
Rivero-Juárez, Antonio
Pineda, Juan Antonio
Camacho, Ángela
Macías, Juan
Laplana Lafaja, Marina
Konieczny, Piotr
Márquez, Francisco J.
Souto, Juan Carlos
Soria, José Manuel
Saulle, Irma
Lo Caputo, Sergio
Biasin, Mara
Rivero, Antonio
Fibla Palazón, Joan
Caruz, Antonio
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Herrero, Rocío; Real, Luis M.; Rivero-Juárez, Antonio; Pineda, Juan Antonio; Camacho, Ángela; Macías, Juan; ... Caruz, Antonio. (2015) . Association of complement receptor 2 polymorphisms withinnate resistance to HIV-1 infection. Genes and Immunity, 2015, vol. 16, p. 134-141. https://doi.org/10.1038/gene.2014.71.
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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 2.6x10-5 (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.Genes and Immunity advance online publication, 8 January 2015; doi:10.1038/gene.2014.71.
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http://hdl.handle.net/10459.1/67997
DOI
https://doi.org/10.1038/gene.2014.71
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Genes and Immunity, 2015, vol. 16, p. 134-141
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