ABCG2 Gene Polymorphisms as Risk Factors for Atorvastatin Adverse Reactions: A Case–Control Study

Abstract

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.

Keywords::

• ABCG2
• adverse drug reactions
• atorvastatin
• CYP3A4
• gene polymorphism
• SLCO1B1

Financial & competing interests disclosure

Work presented in this article was partly sponsored by the Croatian Medicine Agency. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

Work presented in this article was partly sponsored by the Croatian Medicine Agency. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.