Coronary artery disease and the risk-associated LPA variants, rs3798220 and rs10455872, in patients with suspected familial hypercholesterolaemia.

BACKGROUND

The rs3798220 and rs10455872 single nucleotide polymorphisms (SNPs) in LPA are associated with increased plasma concentrations of lipoprotein(a) [Lp(a)] and coronary artery disease (CAD).

METHODS

We investigated the association between rs3798220 and rs10455872 and prevalent CAD in 763 patients with suspected familial hypercholesterolaemia (FH). The rs3798220 and rs10455872 SNPs in LPA were detected using a SEQUENOM platform.

RESULTS

Both LPA SNPs were significantly associated with CAD, but only rs3798220 after adjustment for other risk factors (odds ratio [OR] 2.05; 95% confidence interval [CI] 1.02-4.12; p = 0.045), and neither after adjustment for Lp(a) concentrations. Both SNPs were positively and independently associated with increased Lp(a) (rs3798220: OR 1.27; 95% CI 0.96-1.57; p < 0.001. rs10455872: OR 1.41; 95% CI 1.24-1.58; p < 0.001). Plasma concentrations of Lp(a) were independently associated with prevalent CAD (OR 1.28; 95% CI 1.08-1.52, p = 0.005) after adjustment for LPA SNPs and other cardiovascular risk factors. While both the rs3798220 and rs10455872 SNPs were associated with Lp(a) concentrations and prevalent CAD in patients with suspected FH, this was not independent of Lp(a) concentration.

CONCLUSIONS

Quantification of Lp(a) is more likely to be useful than assessment of these Lp(a)-associated SNPs to augment CAD risk prediction.