title: Association of complement receptor 2 polymorphisms with innate resistance to HIV-1 infection.
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.
authors.affiliation: Immunogenetics Unit, Department of Experimental Biology, University of Jaen, Jaen, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Herrero
authors.affiliation: Infectious Diseases and Microbiology Clinical Unit. Valme Hospital, Seville, Spain.
authors.forename: L M
authors.initials: LM
authors.lastname: Real
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital, Cordoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rivero-Juárez
authors.affiliation: Infectious Diseases and Microbiology Clinical Unit. Valme Hospital, Seville, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Pineda
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital, Cordoba, Spain.
authors.forename: Á
authors.initials: Á
authors.lastname: Camacho
authors.affiliation: Infectious Diseases and Microbiology Clinical Unit. Valme Hospital, Seville, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Macías
authors.affiliation: Human Genetics Unit, Department of Basic Medical Sciences, University of Lleida IRBLleida, Lleida, Catalonia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Laplana
authors.affiliation: Immunogenetics Unit, Department of Experimental Biology, University of Jaen, Jaen, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Konieczny
authors.affiliation: Immunogenetics Unit, Department of Experimental Biology, University of Jaen, Jaen, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Márquez
authors.affiliation: Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i de Sant Pau, Barcelone, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Souto
authors.affiliation: Institut d'Investigació Biomèdica Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i de Sant Pau, Barcelone, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Soria
authors.affiliation: Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Saulle
authors.affiliation: Maria Annunziata Hospital, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Lo Caputo
authors.affiliation: Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Biasin
authors.affiliation: Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/Reina Sofia University Hospital, Cordoba, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rivero
authors.affiliation: Human Genetics Unit, Department of Basic Medical Sciences, University of Lleida IRBLleida, Lleida, Catalonia, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Fibla
authors.affiliation: Immunogenetics Unit, Department of Experimental Biology, University of Jaen, Jaen, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Caruz
mesh_terms: D015331:Cohort Studies; D004198:Disease Susceptibility / Q000276:immunology; D015483:HIV Antibodies / Q000235:genetics; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017464:Receptors, Complement 3d / Q000235:genetics* / Q000276:immunology*
chemical_list: D015483:HIV Antibodies; D017464:Receptors, Complement 3d