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Abstract No. THPDB0103

Abstract No. THPDB0103. Polymorphisms in SLC34A1 and ABCC2 genes are related with altered renal tubular function in HIV patients receiving Tenofovir.

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Abstract No. THPDB0103

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  1. Abstract No. THPDB0103 Polymorphisms in SLC34A1 and ABCC2 genes are related with altered renal tubular function in HIV patients receiving Tenofovir. Alvarez E1, Owen A2, Martín Carbonero L3, Siccardi M2, Valencia E2, Moreno V2, Fernández O1, Cuenca L1, and Rodríguez-Nóvoa S1 1Genetic and Molecular Biology Laboratory, Hosp.Univ. La Paz-HCIII, Madrid, Spain, 2Departament of Molecular and Clinical Pharmacology, Univ. Liverpool, UK and 3Infectious Diseases Department, Hosp. Univ. La Paz-HCIII, Madrid, Spain Background: • Kidney tubular dysfunction (KTD) has been associated with long term TDF exposure, urine phosphate wasting being one of the earliest clinical manifestations of KTD. • Variability in the characteristics and severity of KTD might be influenced by host genetic factors. Objective To examine the association between host single nucleotide polymorphisms (SNPs) and abnormal tubular reabsorption of phosphate (TRP)

  2. Methods: NPT2a • Retrospective case-control study. • Accordingly with TRP value: cases TRP <0.82 and controls TRP >0.82 • 20 SNPS were studied in 6 genes potentially affecting TDF-PK and Phosphate tubular reabsorption. • All SNPs were analyzed using Taqman probes. Haplotypes were constructed using PHASE software TFV Results (I) P-gp • 96 HIV patients were included: 39 cases and 57 controls • Cases were longer exposed to TDF: 43 vs 24 months, p=0.01 TDF MPR4 OAT1 Blood Renal Tubular Cell Urine Pi TDF P-gp TFV TDF TDF TFV TFV OAT3 OAT4 Enterocyte Intestinal lumen MRP2

  3. Results (II) • Single SNP analysis: Normal TRP Abnormal TRP 54% 46% 30% 23% p =0.053 p =0.03 CC CT/TT CC CT/TT GenotypeABCC4, rs899494 Genotype SLC34A1, rs3812036

  4. Results (II) • Haplotype analysis: Normal TRP Abnormal TRP p =0.03 p =0.048 48% 54% 28% 28% AnyOther AnyOther TG CGTC HaplotypeABCC2 HaplotypeSLC34A1 Variables independently associated with abnormal TRP Adjustementforage, gender, ethnicity, BMI, HIV RNA, CD4+ T-cells, concomitant ARV and other nephrotoxic drugs Conclusion Monitoring phosphate wasting and screening for genetic polymorphisms could be useful for early identification of patients at higher risk of developing KTD.

  5. Thank you!!

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