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Proximal tubular dysfunction related to tenofovir in people living with HIV/AIDS: a pharmacogenetic study.
Soares, Rita De Cassia Albuquerque; De Araújo, Paulo Sérgio Ramos; Brandão, Lucas André Cavalcanti; Coelho, Antônio Victor Campos; Lima, Kledoaldo; De Melo, Heloisa Ramos Lacerda.
Afiliación
  • Soares RCA; Infectology Sector, Hospital Das Clínicas, Federal University of Pernambuco.
  • De Araújo PSR; Postgraduate At Tropical Medicine, Hospital Das Clínicas, Federal University of Pernambuco.
  • Brandão LAC; Infectology Sector, Hospital Das Clínicas, Federal University of Pernambuco.
  • Coelho AVC; Aggeu Magalhães Institute - Oswaldo Cruz Foundation.
  • Lima K; Pathology Department, Federal University Of Pernambuco.
  • De Melo HRL; Immunopathology Laboratory, Federal University of Pernambuco, Recife - PE.
Pharmacogenet Genomics ; 32(9): 293-300, 2022 12 01.
Article en En | MEDLINE | ID: mdl-36256702
OBJECTIVES: The purpose of this case-control study was to verify the association between single nucleotide polymorphisms (SNPs) in genes encoding drug transporters related to tenofovir disoproxil fumarate (TDF) and proximal renal tubular dysfunction (PRTD), and the association between PRTD and clinical characteristics. METHODS: The 'cases' met the diagnostic criteria for PRTD, determined by the presence of two or more of the following abnormalities: non-diabetic glycosuria, metabolic acidosis, increased uric acid and phosphorus excretion, decreased tubular phosphorus reabsorption and ß2-microglobulinuria. We analyzed eight SNPs in ABCC2, ABCC4, ABCC10 and SLC28A2 genes. Genotyping was performed using real-time PCR. RESULTS: Of the 204 people living with HIV, 38 (18.6%) met the criteria for diagnosis of PRTD and 131 were male (64.2%), with a mean age of 49 years and a history of previous antiretroviral therapy for an average of 5 years. In the multivariate analysis, older individuals, TDF use, protease inhibitor, antihypertensives and anticonvulsants were associated with a risk of developing PRTD. Increased excretion of ß2microglobulin was associated with the A/G genotype of rsCC8187710 from ABCC2 ( P = 0.003) and the following genotypes of ABCC4 SNPs: A/G from rs1059751 ( P = 0.023), G/G from rs1059751 ( P = 0.030) and C/C of rs3742106 ( P = 0.041). The increase in the fraction of excreted phosphorus was associated with the C/T genotype of SNCC rsP40037 from ABCC2 ( P = 0.0041). CONCLUSIONS: The results indicate an important relationship between SNPs associated with these markers and changes in proximal renal tubule function, and thus support their use as biomarkers for the early detection of PRTD risk.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Síndrome de Inmunodeficiencia Adquirida / Fármacos Anti-VIH Tipo de estudio: Observational_studies / Risk_factors_studies / Screening_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Pharmacogenet Genomics Asunto de la revista: FARMACOLOGIA / GENETICA MEDICA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por VIH / Síndrome de Inmunodeficiencia Adquirida / Fármacos Anti-VIH Tipo de estudio: Observational_studies / Risk_factors_studies / Screening_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Pharmacogenet Genomics Asunto de la revista: FARMACOLOGIA / GENETICA MEDICA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos