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2015 ; 10
(11
): e0141931
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Drug Transporter Genetic Variants Are Not Associated with TDF-Related Renal
Dysfunction in Patients with HIV-1 Infection: A Pharmacogenetic Study
#MMPMID26535588
Nishijima T
; Hayashida T
; Kurosawa T
; Tanaka N
; Oka S
; Gatanaga H
PLoS One
2015[]; 10
(11
): e0141931
PMID26535588
show ga
OBJECTIVE: To investigate whether single nucleotide polymorphisms (SNP) of drug
transporter proteins for TDF is a risk factor for TDF-related renal function
decrement. METHODS: This study investigated the association between 3 SNPs
(ABCC2-24, 1249, and ABCB1 2677), which are shown to be associated with
TDF-induced tubulopathy, and clinically important renal outcomes
(>10ml/min/1.73m2 decrement in eGFR relative to baseline, >25% decrement in eGFR,
and eGFR <60ml/min/1.73m2) in 703 HIV-1-infected Japanese patients who initiated
TDF-containing antiretroviral therapy (ART). Genotyping was performed by allelic
discrimination using TaqMan 5'-nuclease assays. RESULTS: 95% of the study
patients were males and 66% were treatment-naïve, with median CD4 count of
249/?l, median baseline eGFR of 96ml/min/1.73m2 (IQR 84.6-109.2), and median
exposure to TDF of 3.66 years (IQR 1.93-5.59). The frequencies of genotypes at
-24, 1249 of ABCC2, and 2677 of ABCB1 were neither different between patients
with decrement in eGFR of >10ml/min/1.73m2 and those without such decrement
(ABCC2: -24, p = 0.53, 1249, p = 0.68; ABCB1: 2677, p = 0.74), nor between those
without and with the other two renal outcomes (>25% decrement: ABCC2: -24, p =
0.83, 1249, p = 0.97, ABCB1: 2677, p = 0.40; eGFR <60ml/min/1.73m2: ABCC2: -24, p
= 0.51, 1249, p = 0.81, ABCB1: 2677, p = 0.94). Logistic regression analysis
showed that the risk genotype of the three SNPs were not associated with any of
the three renal outcomes, respectively. Logistic regression model that applied
either dominant, recessive, or additive model yielded the same results.
CONCLUSIONS: SNPs of the drug transporters for TDF are not associated with
clinically important renal outcomes in patients who initiated TDF-containing ART.