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


METHODS
We 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.


RESULTS
For 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.


CONCLUSIONS
The rs3798220 and rs10455872 SNPs explain the association of the CCTC and CTTG haplotypes with CHD.
Shiffman
Dov
D
Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA. dov.shiffman@celera.com
Louie
Judy Z
JZ
Rowland
Charles M
CM
Malloy
Mary J
MJ
Kane
John P
JP
Devlin
James J
JJ
D053241:Apoprotein(a) / Q000235:genetics*; D002140:California; D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
D053241:Apoprotein(a)