This study evaluated the impact of seven single nucleotide polymorphisms in five candidate genes (ABCB1, ABCC2, ABCC4, SLC22A6, and SLC22A11) in relation to nephrotoxicity associated with highly active antiretroviral therapy (HAART) in HIV-infected individuals.
The following single nucleotide polymorphisms were genotyped by real-time PCR: ABCB1 rs1045642, ABCC2 rs717620 and rs2273697, ABCC4 rs1751034 and rs3742106, SLC22A6 rs11568626, and SLC22A11 rs11231809 in 507 HIV-infected patients from the city of Porto Alegre, Southern Brazil, receiving HAART for, at least, 1 year.
From the 507 HIV-infected patients recruited, 19.1% presented a reduction in estimated glomerular filtration rate (eGFR). A total of 16 (3.2%) patients fulfilled the criteria for chronic kidney disease (defined as eGFR<60 ml/min/1.73 m2). Individuals carrying at least one T allele of ABCC2 −24 C>T (rs717620) presented lower eGFR than C/C homozygotes (104±22 vs. 108±22 ml/min/1.73 m2, independent-samples t-test, P=0.040). In multivariate analysis, the predictors associated with decreased eGFR were time of treatment, tenofovir use, atazanavir/ritonavir use, and carrying one T allele of ABCC2 −24 C>T.
Our data support the importance of genetic factors in the etiology of nephrotoxicity in patients treated with HAART. Studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.
aGraduate Program in Pathology
bGraduate Program in Health Sciences, Federal University of Health Sciences of Porto Alegre
cHospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (www.pharmacogeneticsandgenomics.com).
Correspondence to Vanessa S. Mattevi, PhD, Programa de Pós-Graduação em Patologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Rua Sarmento Leite, 245, Sala 309, 90050-170 Porto Alegre, RS, Brazil Tel: +55 51 3303 8763; fax: +55 51 3303 8718; e-mail: firstname.lastname@example.org
Received November 25, 2014
Accepted July 22, 2015