Rúbia Marília de Medeiros1,2, Carolina Fialho Menti3, Jéssica Louise Benelli4, Maria Cristina Cotta Matte1,2, Marineide Gonçalves de Melo5, Sabrina Esteves de Matos Almeida1,2,6, Marilu Fiegenbaum4,+
1Fundação Estadual de Produção e Pesquisa, Centro de Desenvolvimento Científico e Tecnológicos, Porto Alegre, RS, Brasil
2Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brasil
3Universidade Federal de Ciências da Saúde de Porto Alegre, Faculdade de Biomedicina, Porto Alegre, RS, Brasil
4Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-Graduação em Patologia, Porto Alegre, RS, Brasil
5Nossa Senhora da Conceição Hospital, Serviço de Doenças Infecciosas, Porto Alegre, RS, Brasil
6Universidade Feevale, Novo Hamburgo, Brasil
BACKGROUND The time of progression towards AIDS can vary greatly among seropositive patients, and may be associated with host genetic variation. The NR1I2 (PXR) gene, a ligand-activated transcription factor, regulates the transcription immune pathway genes and can therefore be targets of viral replication mechanisms influencing time of progression to AIDS.
OBJECTIVE To verify the association of single nucleotide polymorphisms (SNPs) rs3814057, rs6785049, rs7643645, and rs2461817 in the NR1I2 (PXR) gene with progression to AIDS in HIV-1 infected patients.
METHODS Blood samples were obtained from 96 HIV-1 positive individuals following informed consent. DNA was isolated and genotyped through real time polymerase chain reaction (PCR) for the presence of SNPs in the NR1I2. Questionnaires on socio-demographic features and behaviors were answered and time of progression to AIDS was estimated based on medical chart analysis.
FINDINGS Patients with the GG genotype for rs7643645 were shown to be related with a more rapid disease progression when compared to GA and AA genotypes. This result was maintained by the Multivariate Cox Regression considering sex, ethnicity, and presence of HLA-B*57, HLA-B*27, and CCR5del32 polymorphisms.
MAIN CONCLUSIONS Recent studies reported the expression of the nuclear receptors in T-Lymphocytes, suggesting their possible role in the immune response. In addition, nuclear receptors have been shown to inhibit the HIV replication, although no such mechanism has been thoroughly elucidated to date. This is the first time an association between NR1I2 polymorphism and time of progression to AIDS is reported and supports an apparent relationship between the gene in the immune response and identifies another genetic factor influencing AIDS progression.
Financial support: CNPq (Grant 480431/2007-8), FAPERGS/PPSUS 002/2013 (Grant 1304-2551/13-9).
Received 22 August 2016
Accepted 27 December 2016