Impact of Apolipoprotein A5 Variants on Statin Treatment Efficacy

Abstract

Aims: Despite the fact that statin treatment efficacy is very high, there are substantial differences in treatment effectiveness among individuals. It is supposed that genetic predisposition plays an important role in these differences, but the contribution of individual polymorphisms is poorly understood. So far, more than 30 genes have been examined with ambiguous results. Apolipoprotein A5 is an important determinant of plasma lipid concentrations and its genetic variation could account for some of the observed differences in the response to statin therapy. However, this has not been analyzed before. Materials and methods: We examined the putative association between APOA5 SNPs (c.-1131T>C, c.56C>G and c.457G>A) and efficacy during 3 months of statin treatment in 187 adult Caucasians. Patients were treated with low-dose (10 or 20 mg per day) simvastatin (46.3%), atorvastatin (40.5%) and lovastatin (13.2%). Results: The decrease in cholesterol was not significantly associated with the type or dose of statin. Carriers of the APOA5 genotype TT-1131 (n = 154) benefited more from statin treatment when compared with the C-1131 allele carriers (n = 33) (Δ low-density lipoprotein cholesterol: -36.3 ± 15.1% vs Δ low-density lipoprotein cholesterol: -29.9 ± 12.5%; p < 0.005, Mann-Whitney test). This result was independent of sex, age, BMI and APOE polymorphism. Conclusion: Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment.

KEYWORDS::

• apolipoprotein A5
• cholesterol
• effect
• pharmacogenetics
• polymorphism
• statin
• triglyceride

Acknowledgements

This work was supported by research grant No. 9411–3 (IGA MH-CR). The patients are acknowledged for their participation in the study.

Financial disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with financial interest in, or financial conflict with the subjects matters or materials used in the manuscript. This includes employments, consultancies, honoraria, stock ownership or options, expert testimony, grant or patents receiving or pending, or royalties.

No writing assistance was utilized in the production of the 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

This work was supported by research grant No. 9411–3 (IGA MH-CR). The patients are acknowledged for their participation in the study.