Dataset Information

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

ABSTRACT: 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).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).These results indicate that ABCB1 rs2032582 may predict the risk of AILI in Japanese population.

SUBMITTER: Fukunaga K

PROVIDER: S-EPMC4906899 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Fukunaga Koya K Nakagawa Hiroshi H Ishikawa Toshihisa T Kubo Michiaki M Mushiroda Taisei T

BMC genetics 20160613 1

<h4>Background</h4>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).<h4>Results</h4>An SNP in ABCB1 (rs2032582: 2677G > T/A) was significantly associated with ...[more]

PMID: 27296832

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Project description:Abstract Objectives Nonalcohol fatty liver disease (NAFLD) is one of the considerable health problems in the world. NAFLD is a representative phenotype in the liver reflecting individual's lifestyle. Previous studies suggested that a single nucleotide polymorphism (SNP) in the CD36 gene was associated with dietary fat intake and fat metabolism. Therefore, we hypothesized that this SNP may be associated with fatty liver (FL) and NAFLD. We conducted this cross-sectional study to examine the association between two CD36 polymorphisms (rs1761667 and rs1527483) and FL and NAFLD in a Japanese population. Methods A total of 525 local residents participated in the health check-up in Yakumo town, Hokkaido, Japan. This cross-sectional study was conducted based on clinical information collected in this health check-up. Among all participants, 57 people were excluded due to the inadequate informed consent, clinical history of liver disease. Genotyping of two polymorphisms in the CD36 gpgbrkkene was performed by using the PCR-CTPP method. Ultrasound examination was performed by four qualified ultrasonographers. In this present, NAFLD was defined as 1) presence of FL and 2) a daily alcohol consumption <10 g in women and <20 g in men. Multivariable regression analysis was performed after adjusting for age, sex, waist circumference, medicine for dyslipidemia. Results The mean age of participants was 63.4 (10.0). The minor allele frequency of rs1761667 and rs1527483 was 0.26 and 0.21, respectively. The presence of FL and NAFLD was 90 (19.2%) and 67 (14.3%), respectively. Multiple regression analyses showed a significant association between rs1761667 and presence of FL (P = 0.04), and FL grade (P = 0.03). However, rs1761667 was not significantly associated with NAFLD (P = 0.11). No significant associations were found between rs1527483 and FL and NAFLD. Conclusions A polymorphism (rs1761667) in the CD36 gene was associated with the presence of FL, but we did not find a significant association between this SNP and NAFLD. Funding Sources This study was supported by the Mishima Kaiun Memorial Foundation.

Dataset Information

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

Publications

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

Similar Datasets

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