Single variants can explain the association between coronary heart disease and haplotypes in the apolipoprotein(a) locus

ObjectiveLPA encodes apolipoprotein(a), and a CCTC haplotype in the LPA locus is associated with CHD. The 4399Met variant (rs3798220) of LPA has a risk estimate for CHD similar to that of the CCTC haplotype. We asked whether co-incidence with the 4399Met variant explained the association of the haplotype with CHD.MethodsWe stratified by the 4399Met variant and another LPA SNP (rs10455872) associated with CHD and tested the association between CHD and 4 SNPs that define two haplotypes associated with CHD: CCTC and CTTG.ResultsFor CCTC, in the presence of the rs3798220 risk allele the OR was 1.68 (95% CI: 1.05–2.68, P = 0.03) versus 0.30 (95% CI: 0.06–1.59, P = 0.16) with the non-risk allele. For CTTG, in the presence of the rs10455872 risk allele the OR was 1.57 (95% CI: 1.15–2.13, P = 0.004) versus 1.04 (95% CI: 0.79–1.35, P = 0.77) with the non-risk allele.ConclusionThe rs3798220 and rs10455872 SNPs explain the association of the CCTC and CTTG haplotypes with CHD.