title: Drug Transporter Genetic Variants Are Not Associated with TDF-Related Renal Dysfunction in Patients with HIV-1 Infection: A Pharmacogenetic Study.
abstract: 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/μl, 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.
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.|Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishijima
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Tsunefusa
authors.initials: T
authors.lastname: Hayashida
authors.affiliation: Department of Mathematical Science for Information Sciences, Graduate School of Science, Tokyo University of Science, Tokyo, Japan.|Biostatistics Section, Department of Clinical Research and Informatics, Clinical Science Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Kurosawa
authors.affiliation: Biostatistics Section, Department of Clinical Research and Informatics, Clinical Science Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.|Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.|Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology*; D016015:Logistic Models; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D019380:Anti-HIV Agents; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000068698:Tenofovir; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human