Gene variants may influence NSAID-induced coronary risk
MedWire News: Variants in the prostaglandin-endoperoxide synthase-1 (PTGS1) and C-reactive protein (CRP) genes may influence the risk for acute coronary events associated with non-steroidal antiinflammatory drugs (NSAID), Canadian researchers believe.
However, they admit that their findings, which appear in the American Journal of Cardiology, are preliminary and require confirmation in larger cohorts.
James Brophy (McGill University, Montreal, Quebec, Canada) and team tested the hypothesis that gene–drug interactions modulate the cardiovascular risk associated with cyclooxygenase-2-selective (coxibs) and nonselective NSAIDs.
“The biologic mechanism that triggers these cardiovascular events is still unclear,” they write. “The favored hypothesis centers on a potential disequilibrium in prostaglandin synthesis between prothrombotic thromboxane A2 and antithrombotic prostacyclin.”
From a registry of patients with acute coronary syndromes, the team identified 115 patients exposed to NSAIDs and 345 nonexposed patients matched for age, gender, and hospital. All participants were genotyped for 115 candidate single nucleotide polymorphisms (SNPs).
In the primary analysis of patients exposed to any NSAID, the largest odds ratios (ORs) for NSAID exposure were observed for two SNPs in the PTGS1 gene (rs10306135 and rs12353214), at 7.33 and 4.77, respectively.
Significant associations with NSAID exposure were also observed with two SNPs in the matrix metalloproteinase-1 (MMP1) gene, two SNPs in the angiotensinogen (AGT) gene, one SNP in the chromosome 9p21.3 region, one SNP in the klotho (KL) gene, and one SNP in the CRP gene.
In an analysis restricted to coxib-exposed patients and their matched controls, statistically significant associations were observed between NSAID exposure and five SNPs at four loci: PTGS1, chromosome 9p21.3, CRP, and KL.
For the two SNPs in the PTGS1 gene, the odds ratios associated with NSAID use were 6.94 and 7.11, respectively. For the SNP in the CRP gene (rs1205), the odds ratio associated with NSAID use was 1.64.
Noting that there is currently no way to identify patients at increased risk for NSAID-associated cardiac events, Brophy et al write: “Our study provides justification for the further investigation of genes that may be linked to the cardiovascular risk of NSAIDs.
“The ability to identify patients with an increased predisposition to this risk would be clinically meaningful and of great public health importance.”
However, they add: “Additional case-control and cohort studies are necessary to confirm the independence of genotype and exposure and to verify these provocative findings.”
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By Joanna Lyford