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
N1 - Publisher Copyright:
© 2016 The Author(s).
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
SN - 1471-2156
VL - 17
JO - BMC Genetics
JF - BMC Genetics
IS - 1
M1 - 79
ER -