title: Association of single nucleotide polymorphisms in the lens epithelium-derived growth factor (LEDGF/p75) with HIV-1 infection outcomes in Brazilian HIV-1+ individuals.
abstract: The lens epithelium-derived growth factor p75 (LEDGF/p75), coded by the PSIP1 gene, is an important host co-factor that interacts with HIV-1 integrase to target integration of viral cDNA into active genes. The aim of this study was to investigate the association of SNPs in the PSIP1 gene with disease outcome in HIV-1 infected patients. We performed a genetic association study in a cohort of 171 HIV-1 seropositive Brazilian individuals classified as rapid progressors (RP, n = 69), typical progressors (TP, n = 79) and long-term nonprogressors (LTNP, n = 23). The exonic SNP rs61744944 and 9 tag SNPs were genotyped. A group of 192 healthy subjects was analyzed to determine the frequency of SNPs and haplotypes in the general population. Linkage disequilibrium (LD) analyses indicated that the SNPs analyzed were not in high LD (r2<0.8). Logistic regression models suggested that patients carrying the T allele rs61744944 (472L) were more likely to develop a LTNP phenotype (OR = 4.98; p = 0.05) as compared to TP group. The same trend was observed when LTNPs were compared to the RP group (OR = 3.26). Results of haplotype analyses reinforced this association, since the OR values obtained for the haplotype carrying allele T at rs61744944 also reflected an association with LTNP status (OR = 6.05; p = 0.08 and OR = 3.44; p = 0.12 for comparisons to TP and RP, respectively). The rare missense variations Ile436Ser and Thr473Ile were not identified in the patients enrolled in this study. Gene expression analyses showed lower LEDGF/p75 mRNA levels in peripheral blood mononuclear cells obtained from HIV-1 infected individuals. However, these levels were not influenced by any of the SNPs investigated. In spite of the limited number of LTNPs, these data suggest that the PSIP1 gene could be associated with the outcome of HIV-1 infection. Further analyses of this gene may guide the identification of causative variants to help predict disease course.
authors.affiliation: Laboratório de AIDS e Imunologia Molecular, IOC/FIOCRUZ, Rio de Janeiro, Brasil.
authors.forename: Caroline Pereira Bittencourt
authors.initials: CP
authors.lastname: Passaes
authors.affiliation: Laboratório de Virologia Molecular Animal, Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Cynthia Chester
authors.initials: CC
authors.lastname: Cardoso
authors.affiliation: Laboratório de AIDS e Imunologia Molecular, IOC/FIOCRUZ, Rio de Janeiro, Brasil.
authors.forename: Diogo Gama
authors.initials: DG
authors.lastname: Caetano
authors.affiliation: Laboratório de AIDS e Imunologia Molecular, IOC/FIOCRUZ, Rio de Janeiro, Brasil.
authors.forename: Sylvia Lopes Maia
authors.initials: SL
authors.lastname: Teixeira
authors.affiliation: Laboratório de AIDS e Imunologia Molecular, IOC/FIOCRUZ, Rio de Janeiro, Brasil.
authors.forename: Monick Lindenmeyer
authors.initials: ML
authors.lastname: Guimarães
authors.affiliation: Instituto de Pesquisa Clínica Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brasil.
authors.forename: Dayse Pereira
authors.initials: DP
authors.lastname: Campos
authors.affiliation: Instituto de Pesquisa Clínica Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brasil.
authors.forename: Valdilea Gonçalves
authors.initials: VG
authors.lastname: Veloso
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Miller School of Medicine, University of Miami, Miami, United States of America.
authors.forename: Dunja Z
authors.initials: DZ
authors.lastname: Babic
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Miller School of Medicine, University of Miami, Miami, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Stevenson
authors.affiliation: Laboratório de Hanseníase, IOC/FIOCRUZ, Rio de Janeiro, Brasil.
authors.forename: Milton Ozório
authors.initials: MO
authors.lastname: Moraes
authors.affiliation: Laboratório de AIDS e Imunologia Molecular, IOC/FIOCRUZ, Rio de Janeiro, Brasil.
authors.forename: Mariza Gonçalves
authors.initials: MG
authors.lastname: Morgado
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D015497:HIV-1 / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016662:Virus Integration; D055815:Young Adult
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor