Association of single nucleotide polymorphisms in the lens epithelium-derived growth factor (LEDGF/p75) with HIV-1 infection outcomes in brazilian HIV-1+ individuals

dc.creatorPassaes, Caroline Pereira Bittencourt
dc.creatorCardoso, Cynthia Chester
dc.creatorCaetano, Diogo Gama
dc.creatorTeixeira, Sylvia Lopes Maia
dc.creatorGuimarães, Monick Lindenmeyer
dc.creatorCampos, Dayse Pereira
dc.creatorVeloso, Valdiléa G.
dc.creatorBabic, Dunja Z.
dc.creatorStevenson, Mario
dc.creatorMoraes, Milton Ozório
dc.creatorMorgado, Mariza Gonçalves
dc.date2015-05-18T15:47:45Z
dc.date2015-05-18T15:47:45Z
dc.date2014
dc.date.accessioned2023-09-26T20:48:57Z
dc.date.available2023-09-26T20:48:57Z
dc.identifierPASSAES, Caroline Pereira Bittencourt et al. Association of single nucleotide polymorphisms in the lens epithelium-derived growth factor (LEDGF/p75) with HIV-1 infection outcomes in brazilian HIV-1+ individuals. Plos One, v. 9, n. 7, p. 1-8, July 2014.
dc.identifier1932-6203
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/10382
dc.identifier10.1371/journal.pone.0101780
dc.identifier1932-6203
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8864380
dc.descriptionCNPq, FAPERJ, NIH
dc.descriptionThe 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectAcquired Immunodeficiency Syndrome
dc.subjectHIV Infections
dc.subjectAntigens, CD4
dc.subjectHIV-1
dc.subjectSíndrome de Imunodeficiência Adquirida
dc.subjectInfecções por HIV
dc.subjectAntígenos CD4
dc.subjectHIV-1
dc.titleAssociation of single nucleotide polymorphisms in the lens epithelium-derived growth factor (LEDGF/p75) with HIV-1 infection outcomes in brazilian HIV-1+ individuals
dc.typeArticle


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