Key result
Common CASQ2, GPD1L, and NOS1AP variants linked to higher SCD risk in CAD patients.
Why the study?
Recent evidence suggests a genetic component for sudden cardiac death in subjects with coronary artery disease, but specific gene associations remain to be identified.
Are common genetic variants in CASQ2, GPD1L, and NOS1AP associated with an increased risk of sudden cardiac death in patients with coronary artery disease?
Case-Control (n=979)
No
Are common genetic variants in CASQ2, GPD1L, and NOS1AP associated with an increased risk of sudden cardiac death in patients with coronary artery disease?
p-value: p=0.007 to 0.04
Common genetic variations in or near CASQ2, GPD1L, and NOS1AP are associated with an increased risk of sudden cardiac death in patients with coronary artery disease, suggesting an overlap between rare and common forms of SCD.
Should not yet guide SCD risk assessment in CAD; leaves open validation in prospective cohorts.
BACKGROUND: Recent evidence suggests a genetic component for sudden cardiac death (SCD) in subjects with coronary artery disease (CAD). We conducted a systematic candidate-gene approach using haplotype-tagging single nucleotide polymorphisms (htSNPs) to identify genes associated with SCD risk in the context of CAD. METHODS AND RESULTS: We investigated 1424 htSNPs representing 18 genes with mutations described in patients with ventricular arrhythmias in 291 subjects from the Oregon Sudden Unexpected Death Study (Ore-SUDS). The Ore-SUDS is an ongoing prospective investigation of SCD in the Portland, OR, metropolitan area (population, 1 000 000). SCD cases were ascertained from multiple sources and medical records were reviewed to determine the presence of CAD. A total of 36 SNPs were associated with risk of SCD (uncorrected probability values <0.01) in the initial study sample. These SNPs were subsequently tested for replication in an independent case-control study sample from the Ore-SUDS (n=688). The association analysis in the replication stage revealed 6 SNPs associated with SCD: CASQ2 region (rs17500488, P=0.04; rs3010396, P=0.007; rs7366407; P=0.04), NOS1AP (rs12084280, P=0.04; rs10918859, P=0.02), and 1 SNP located ≈26 kb upstream of GPD1L (rs9862154, P=0.04). CONCLUSIONS: Common variations in or near CASQ2, GPD1L, and NOS1AP are associated with increased risk of SCD in patients with CAD. These findings provide further evidence for overlap between the genetic architecture of rare and common forms of SCD, and replication in additional populations is warranted.
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Westaway et al. (2011) conducted a case-control in Sudden cardiac death in coronary artery disease (n=979). Common variants in CASQ2, GPD1L, and NOS1AP vs. Absence of these variants was evaluated on Sudden cardiac death (p=0.007 to 0.04). Common variations in or near CASQ2, GPD1L, and NOS1AP are significantly associated with an increased risk of sudden cardiac death in patients with coronary artery disease (P=0.007 to P=0.04).
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