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

Genes & Immunity volume 16, pages 134–141 (2015)Cite this article

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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.

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Acknowledgements

This work was supported by Spanish Health Ministry [PI021476, PI051778 and PI10/01232 to JF, JAP and ACar]; Instituto de Salud Carlos III-RETIC [RD06/006 to JAP]; Fundació Marató TV3 [020730 and 020732 to JF and ACar]; Junta de Andalucía [PI-0335/2009 to ACar]; Fundación Progreso y Salud of the Consejería de Salud de la Junta de Andalucía [AI-0021 to JAP]; and Universidad de Jaen [UJA2013/10/03 to ACar].

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Authors and Affiliations

  1. Department of Experimental Biology, Immunogenetics Unit, University of Jaen, Jaen, Spain

    R Herrero, P Konieczny, F J Márquez & A Caruz

  2. Infectious Diseases and Microbiology Clinical Unit. Valme Hospital, Seville, Spain

    L M Real, J A Pineda & J Macías

  3. Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital, Cordoba, Spain

    A Rivero-Juárez, Á Camacho & A Rivero

  4. Department of Basic Medical Sciences, Human Genetics Unit, University of Lleida IRBLleida, Lleida, Catalonia, Spain

    M Laplana & J Fibla

  5. Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i de Sant Pau, Barcelone, Spain

    J C Souto & J M Soria

  6. Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

    I Saulle & M Biasin

  7. Maria Annunziata Hospital, Florence, Italy

    S Lo Caputo

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Correspondence to A Caruz.

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Herrero, R., Real, L., Rivero-Juárez, A. et al. Association of complement receptor 2 polymorphisms with innate resistance to HIV-1 infection. Genes Immun 16, 134–141 (2015). https://doi.org/10.1038/gene.2014.71

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