Abstract
High lipoprotein(a) [Lp(a)] concentrations are one of the most important genetically determined risk factors for coronary artery disease (CAD). Many functional single nucleotide polymorphisms (SNPs) of the LPA gene have pronounced effects on Lp(a) concentrations. Studies show that rs3798220 polymorphism is strongly associated with Lp(a) concentration and also with risk of CAD.
Goal: To evaluate if LPA rs3798220 T>C is associated with CAD beyond its effect on Lp(a) levels.
We performed a case-control study with 3,157 individuals (1,721 CAD patents and 1,436 controls). The LPA rs3798220 T>C was genotyped with the TaqMan PCR assay (Applied Biosystems 7300 Real-Time). This variant has a minor allele frequency (MAF) <2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. Laboratory analysis was performed, and Lp(a) biochemical levels were measured in the cases and controls. Chi-squared tests were used to determine differences by genotype in CAD association (in cases and controls). We also reported a multivariate logistic regression to test if this LPA variant is still independently associated with CAD after adjustment to Lp(a) levels and traditional risk factors for CAD.
Wild-type genotype TT was increased in the group without CAD, whereas the genotype TC was higher in patients with CAD (p<0.0001). After multivariate logistic regression, adjusted for traditional risk factors, the TC genotype remained in the equation as an independent risk factor for CAD (OR=2.36; 95%CI: 1.54–3.61; p<0.0001). When the multivariate regression analysis is adjusted for traditional risk factors plus Lp(a) levels, the TC genotype remains in the equation as independently associated with CAD despite being substantially attenuated (OR=1.67; 95%CI: 1.07–2.60; p=0.025).
Author notes
Funding Acknowledgements: None.
