ABCG2 gene polymorphisms as risk factors for atorvastatin adverse reactions: a case-control study

Aim: To explore the association between dose-related adverse drug reactions (ADRs) of atorvastatin and polymorphisms of ABCG2, taking into account the influence of CYP3A4 and SLCO1B1 genes. Materials & methods: Sixty patients who experienced atorvastatin dose-related ADRs and 90 matched patients without ADRs were enrolled in the study. Genotyping for ABCG2 421C > A, CYP3A4*22, SLCO1B1 388A > G, SLCO1B1 521T > C variants was performed by real-time PCR. Results: Patients with ABCG2 421CA or AA genotypes had 2.9 times greater odds of developing atorvastatin dose-dependent ADRs (OR: 2.91; 95% CI: 1.22-6.95; p = 0.016) than those with ABCG2 421CC genotype. After adjustments for clinical and genetic risk factors, ABCG2 remained a statistically significant predictor of adverse drug reactions (OR: 2.75; 95% CI: 1.1-6.87; p = 0.03;). Also, carriers of SLCO1B1 521 TC or CC genotypes had 2.3 greater odds (OR: 1.03-4.98; 95% CI: 1.03-4.98; p = 0.043) of experiencing ADRs caused by atorvastatin in comparison with carriers of SLCO1B1 521 TT genotype. Conclusion: Our study demonstrated an association between atorvastatin-induced ADRs and genetic variants in the ABCG2 gene.