Differential Lipid Response to Statins Is Associated With Variants in the BUD13–APOA5 Gene Region

Abstract

Genetic variants within the BUD13-APOA5 gene region are known to be associated with high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels. Recent studies suggest that single-nucleotide polymorphisms (SNPs) within this region affect HDL-C response to statin-fibrate combination therapy and low-density lipoprotein cholesterol (LDL-C) response to statin therapy. We hypothesized that SNPs within the BUD13-APOA5 region are associated with TG, HDL-C, and LDL-C response to statin therapy. We examined 1520 observations for 1086 patients from the Personalized Medicine Research Project, a large biorepository at the Marshfield Clinic Research Foundation, who had received statin therapy and been previously genotyped for polymorphisms in the 11q23 chromosomal region. A significant differential response to statin therapy was observed for three SNPs. The minor allele at rs11605293 significantly attenuated TG-lowering response to pravastatin (P=1.59E-04) while the minor allele at rs12806755 was associated with a similar response to lovastatin (P=1.92E-04). Genotypes at rs947990 significantly attenuated LDL-C reduction to atorvastatin therapy (P=6.68E-04) with some patients with the minor allele having LDL-C increase following therapy. No SNPs within the BUD13-APOA5 region were associated with a significant effect on HDL-C reduction in response to statin therapy. In conclusion, this study suggests that common SNPs within the BUD13-APOA5 can affect TG and LDL-C response to statin therapy in a North American population.

Prediction of cholesterol ratios within a Korean population

“…ABCA8 might function as a transporter of lipophilic substrates such as the bioactive lipid leukotriene C4 [ 39 ]. In addition, differential lipid response to statins was observed in a previous association study that used SNPs in the BUD13 – APOA5 gene region [ 40 ]. Further studies may be needed to understand the effects of SNPs on genes and lipid metabolism.…”

Genetic Predictors of Intensive Lipid-Lowering Therapy Efficacy and Its Anti-Inflammatory Effects in Very High Cardiovascular Risk Patients

“…Отмечалось индивидуальное влияние полиморфизмов отдельных генов на эффективность разных статинов. Так, при анализе данных 1086 пациентов были рассмотрены 3 мононуклеотидных полиморфизма BUD13-АРОА5 и выявлено влияние рецессивной аллели rs11605293 на достижение целевого уровня ТГ при терапии правастатином, рецессивной аллели rs12806755 на снижение уровня ТГ при терапии ловастатином, рецессивной аллели rs947990 на эффективность снижения ХС-ЛПНП аторвастатином [13].Также были получены данные о предиктивной значимости в ответе на терапию аторвастатином полиморфизмов ABCB1 (-41A/G), YMGCRSNP 29G/A, rs5908A/G, rs12916C/T и CYP7A1-204A/C [14].…”

“…Выбор вышеуказанных генов был обусловлен их функциональной активностью и предполагаемым возможным влиянием на эффективность терапии статинами. В нескольких исследованиях ранее изучался вклад рассматриваемых аллелей в ответ на липидснижающую терапию у других этнических групп, однако однозначных результатов получено не было [9][10]13].…”

Influence of APOA5 locus on the treatment efficacy of three statins: evidence from a randomized pilot study in Chinese subjects

“…In addition, accumulating evidence suggests that this gene also confers risk for cardiovascular disease (10) and myocardial infarction (17). Although previous studies have suggested a link between this gene and statin treatment (18,19), the impact of the APOA5 locus on the clinical responses to different types of statin therapy is less clear.…”