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Abstract No. THPDB0103

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

Alvarez E1, Owen A2, Martín Carbonero L3, Siccardi M2, Valencia E2, Moreno V2, Fernández O1, Cuenca L1, and Rodríguez-Nóvoa S1

Background:

Variability in the characteristics and severity of KTD might be influenced by host genetic factors.

Kidney tubular dysfunction (KTD) has been associated with long term TDF exposure, urine phosphate wasting being one of the earliest clinical manifestations of KTD.

Polymorphisms in SLC34A1 and ABCC2 genes are related with altered renal tubular function in HIV

patients receiving Tenofovir.

To examine the association between host single nucleotide polymorphisms (SNPs) and abnormal tubular reabsorption of phosphate (TRP)

Objective

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Methods: 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

Results (I) 96 HIV patients were included: 39 cases and 57 controls Cases were longer exposed to TDF: 43 vs 24 months, p=0.01

OAT4

TFV

OAT3

OAT1

TFV

UrineBlood Renal Tubular Cell

NPT2a

TFV

Pi

MRP2

Intestinal lumen Enterocyte

P-gp

TDF

TDF

TDF TFV

P-gp

TDF MPR4

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CC CT/TTGenotype SLC34A1, rs3812036

p =0.03

CC CT/TTGenotype ABCC4, rs899494

p =0.053

Normal TRPAbnormal TRP

Results (II) Single SNP analysis:

30%54% 46%

23%

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P.E, 95% C.I pComorbidities (Hypertension, Diabetes) 3.9 [1.16-13.08] 0.027TDF exposure (months) 1.04 [1.001-1.07] 0.045

Haplotype SLC34A1TG+ABBC2-CGTC 6.5 [1.67-25.36] 0.007

Adjustement for age, gender, ethnicity, BMI, HIV RNA, CD4+ T-cells, concomitant ARV and other nephrotoxic drugs

Monitoring phosphate wasting and screening for genetic polymorphisms could be useful for early identification of patients at higher risk of developing KTD.

Conclusion

Results (II)

Variables independently associated with abnormal TRP

Normal TRPAbnormal TRP

Haplotype SLC34A1 Haplotype ABCC2Any Other TG Any Other CGTC

p =0.03 p =0.048

28%54%

28%48%

Haplotype analysis:

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Thank you!!