Ten SNPs linked with effectiveness of statins to reduce MI risk
MedWire News: Ten single nucleotide polymorphisms (SNPs) in eight genes modify statins' effectiveness in reducing the risk for myocardial infarction (MI), research shows.
The most significant interaction was observed with a variant in the SCARB1 gene, report Anke-Hilse Maitland-van der Zee (Utrecht University, The Netherlands) and colleagues in the journal Atherosclerosis.
Notwithstanding the established efficacy of statins to reduce the risk for cardiovascular disease, various cholesterol pathway-related genes are thought to be responsible for individual responsiveness to statin therapy.
Previous pharmacogenomic studies have examined the cholesterol-lowering response to statin therapy, but few have investigated the effect of genes on clinically important outcomes, the investigators report.
In this study, the researchers investigated the influence of tagging SNPs within candidate genes on the effectiveness of statins in reducing the risk for MI.
They designed a nested case-control study using hospital discharge records of patients involved in Dutch pharmacogenetics studies.
From the 668 MI cases and 1217 controls, the researchers identified 10 SNPs in eight genes found to influence the effectiveness of statin therapy.
The most significant interaction was for SNP rs4765615 in the SCARB1 gene. Homozygous carries of the A allele did not benefit from statin treatment compared with individuals carrying one or two G alleles.
"Despite the unknown underlying mechanism of this gene treatment interaction, our study indicates a role for SCARB1 in the response to statins," state Maitland-van der Zee and colleagues.
Two variants in PCSK9, two variants in ABCG5, and variants in the LIPC, ABCA1, PPARG, LRP1, and SOAT1 genes also significantly interacted with statin.
Only five of the 10 genes found to interact with statin therapy were available in a replication cohort, and none of these genes reached statistical significance for the interaction with clinical outcomes.
The researchers highlight the effect of the PCSK9 E670G polymorphism on statin efficacy; carriers of one or two of the variant alleles did not benefit from statin therapy.
From a clinical perspective, carriers of this variant might "benefit from more aggressive lipid-lowering treatment and could especially benefit from novel hypercholesterolemic therapy strategy of PCSK9 inhibition," state the researchers.
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