Polymorphisms associated with renal adverse effects of antiretroviral therapy in a Southern Brazilian HIV cohort

Autor: Regina Kuhmmer Notti, Eduardo Sprinz, Rosmeri Kuhmmer Lazzaretti, Vanessa Suñé Mattevi, Aline S. Gasparotto, Ivete Terezinha Machado da Rocha
Rok vydání: 2015
Předmět:
Adult
Male
medicine.medical_specialty
ATP Binding Cassette Transporter
Subfamily B
Anti-HIV Agents
Single-nucleotide polymorphism
HIV Infections
Organic Anion Transporters
Sodium-Independent
Kidney
Polymorphism
Single Nucleotide
Nephrotoxicity
Cohort Studies
Organic Anion Transport Protein 1
Gene Frequency
Internal medicine
Antiretroviral Therapy
Highly Active
Genetics
medicine
Humans
General Pharmacology
Toxicology and Pharmaceutics
Renal Insufficiency
Chronic
Molecular Biology
Genetics (clinical)
business.industry
virus diseases
Middle Aged
medicine.disease
Multidrug Resistance-Associated Protein 2
Atazanavir
Regimen
Cohort
Immunology
Molecular Medicine
Ritonavir
Female
Multidrug Resistance-Associated Proteins
business
Brazil
Kidney disease
medicine.drug
Cohort study
Glomerular Filtration Rate
Zdroj: Pharmacogenetics and genomics. 25(11)
ISSN: 1744-6880
Popis: 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 eGFR60 ml/min/1.73 m). Individuals carrying at least one T allele of ABCC2 -24 CT (rs717620) presented lower eGFR than C/C homozygotes (104 ± 22 vs. 108 ± 22 ml/min/1.73 m, 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 CT.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.
Databáze: OpenAIRE
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