論文

査読有り 本文へのリンクあり
2016年1月1日

A single-nucleotide polymorphism in ABCC4 is associated with tenofovir-related beta2-microglobulinuria in Thai patients with HIV-1 infection

PLoS ONE
  • Sirirat Likanonsakul
  • ,
  • Bussakorn Suntisuklappon
  • ,
  • Ravee Nitiyanontakij
  • ,
  • Wisit Prasithsirikul
  • ,
  • Emi E. Nakayama
  • ,
  • Tatsuo Shioda
  • ,
  • Chariya Sangsajja

11
1
開始ページ
e0147724
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0147724
出版者・発行元
PUBLIC LIBRARY SCIENCE

Background In Thailand, the combined generic anti-retroviral drug stavudine/lamivudine/nevirapine (d4T/3TC/NVP) has been used to treat human immunodeficiency virus (HIV)-infected individuals since 2001. Due to relatively frequent adverse effects, d4T gradually has been replaced with tenofovir disoproxil fumarate (TDF). Although the frequency of adverse drug effects with TDF is lower than that with d4T, TDF is known to induce kidney dysfunction, especially in the proximal tubules. It has been reported that renal tubular transporters, including members of the multi-drug resistant (MDR) protein family, are implicated in tenofovir extrusion and may, therefore, confer susceptibility to TDF-induced kidney tubular dysfunction (KTD). We have explored the association between KTD and polymorphisms in genes that encode adenosine triphosphate-binding cassette (ABC)-type MDRs. Methods HIV-infected patients receiving TDF-containing antiretroviral regimens for at least one year were enrolled in the study. The levels of beta2-microglobulin in urine and creatinine (Cr) were measured. Three single-nucleotide polymorphisms, ABCC2 C-24T (rs717620), ABCC2 G1429A (rs2273697), and ABCC4 T4976C (rs1059751), were analyzed using Taq-Man SNP genotyping assays. Results A total of 273 HIV-infected patients were recruited. The median number of years of TDF treatment was 5.04 with interquartile range (IQR) of 3.9-6.7. Despite the length of treatment with TDF, 98.5% patients maintained an estimated glomerular filtration rate (eGFR) of >60 mL/min as calculated by the CKD-EPI formula. Fifty-four patients (19.8%) showed beta2-microglobulinuria (median 2636 ìg/g Cr with IQR of 1519-13197 μg/g Cr). The allele frequency of ABCC4 T4976C among those 54 patients was 0.602, compared to 0.475 among the 219 remaining patients (p = 0.018).

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0147724
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26807589
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000369527800196&DestApp=WOS_CPL
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84959240505&origin=inward 本文へのリンクあり
Scopus Citedby
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ID情報
  • DOI : 10.1371/journal.pone.0147724
  • ISSN : 1932-6203
  • eISSN : 1932-6203
  • PubMed ID : 26807589
  • SCOPUS ID : 84959240505
  • Web of Science ID : WOS:000369527800196

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