ABCB1 polymorphism is associated with atorvastatin-induced liver injury in Japanese population

Koya Fukunaga, Hiroshi Nakagawa, Toshihisa Ishikawa, Michiaki Kubo, Taisei Mushiroda

研究成果: Article査読

20 被引用数 (Scopus)

抄録

Background: To investigate the associations between atorvastatin-induced liver injury (AILI) and polymorphisms in eight genes possibly involved in the hepatic metabolism (CYP2C9, CYP2C19, CYP3A4, CYP3A5 and UGT1A1) and membrane transport (ABCB1, ABCG2 and SLCO1B1) of atorvastatin, we genotyped 30 AILI and 414 non-AILI patients recruited at BioBank Japan for 15 single nucleotide polymorphisms (SNPs). Results: An SNP in ABCB1 (rs2032582: 2677G > T/A) was significantly associated with AILI (P = 0.00068, odds ratio (OR) = 2.59 with 95 % confidence interval (CI) of 1.49-4.50, G allele versus T and A alleles), indicating that the G allele might be a risk factor for AILI. The cytotoxicity test demonstrated that IC50 value of atorvastatin to inhibit the growth and/or viability of Flp-In-293/ABCB1 (2677G) cells was 5.44 ± 0.10 mM, which was significantly lower than those in Flp-In-293/ABCB1 (2677 T) (6.02 ± 0.07 mM) and Flp-In-293/ABCB1 (2677A) cells (5.95 ± 0.08 mM). Conclusions: These results indicate that ABCB1 rs2032582 may predict the risk of AILI in Japanese population.

本文言語English
論文番号79
ジャーナルBMC Genetics
17
1
DOI
出版ステータスPublished - 13-06-2016
外部発表はい

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 遺伝学(臨床)

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