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

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number79
JournalBMC Genetics
Volume17
Issue number1
DOIs
Publication statusPublished - 13-06-2016

Fingerprint

Liver
Wounds and Injuries
Population
Cytochrome P-450 CYP3A
Alleles
Single Nucleotide Polymorphism
Atorvastatin Calcium
Inhibitory Concentration 50
Japan
Odds Ratio
Confidence Intervals
Membranes
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Fukunaga, Koya ; Nakagawa, Hiroshi ; Ishikawa, Toshihisa ; Kubo, Michiaki ; Mushiroda, Taisei. / ABCB1 polymorphism is associated with atorvastatin-induced liver injury in Japanese population. In: BMC Genetics. 2016 ; Vol. 17, No. 1.
@article{78d5e72baac64e7d917cf7d600ed0daf,
title = "ABCB1 polymorphism is associated with atorvastatin-induced liver injury in Japanese population",
abstract = "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.",
author = "Koya Fukunaga and Hiroshi Nakagawa and Toshihisa Ishikawa and Michiaki Kubo and Taisei Mushiroda",
year = "2016",
month = "6",
day = "13",
doi = "10.1186/s12863-016-0390-5",
language = "English",
volume = "17",
journal = "BMC Genetics",
issn = "1471-2156",
publisher = "BioMed Central",
number = "1",

}

ABCB1 polymorphism is associated with atorvastatin-induced liver injury in Japanese population. / Fukunaga, Koya; Nakagawa, Hiroshi; Ishikawa, Toshihisa; Kubo, Michiaki; Mushiroda, Taisei.

In: BMC Genetics, Vol. 17, No. 1, 79, 13.06.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - ABCB1 polymorphism is associated with atorvastatin-induced liver injury in Japanese population

AU - Fukunaga, Koya

AU - Nakagawa, Hiroshi

AU - Ishikawa, Toshihisa

AU - Kubo, Michiaki

AU - Mushiroda, Taisei

PY - 2016/6/13

Y1 - 2016/6/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84973920655&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973920655&partnerID=8YFLogxK

U2 - 10.1186/s12863-016-0390-5

DO - 10.1186/s12863-016-0390-5

M3 - Article

C2 - 27296832

AN - SCOPUS:84973920655

VL - 17

JO - BMC Genetics

JF - BMC Genetics

SN - 1471-2156

IS - 1

M1 - 79

ER -