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

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

doi:https://doi.org/10.1038/gene.2014.71

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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

Suggested citation

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.

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.

URI

http://hdl.handle.net/10459.1/67997

DOI

https://doi.org/10.1038/gene.2014.71

Is part of

Genes and Immunity, 2015, vol. 16, p. 134-141