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Abstract
Elevated levels of lipoprotein(a) are associated with an increased risk of myocardial infarction. Our study aimed to test whether genetic data are consistent with this association being causal. Accordingly, we developed a high-throughput realtime PCR assay to genotype for the lipoprotein(a) kringle IV type 2 (KIV-2) repeat polymorphism in the LPA gene in > 40,000 individuals. The LPA KIV-2 genotype associated with plasma levels of lipoprotein(a) (trend p < 0.001), and the LPA KIV-2 genotype associated with risk of myocardial infarction (trend p < 0.001 to 0.03) in a manner consistent with its effect on plasma levels of lipoprotein(a). The association of LPA KIV-2 genotypes raising plasma levels of lipoprotein(a) with increased risk of myocardial infarction strongly supports a causal association of lipoprotein(a) with risk of myocardial infarction.
Acknowledgements
We thank laboratory technicians Anja Jochumsen and Preben Galasz (Department of Clinical Biochemistry, Herlev Hospital) for excellent technical assistance. This work was supported by The Danish Heart Foundation, IMK Almene Fund, Carl-Bertil Laurell's Nordic Fund for Clinical Chemistry, and Johan and Lise Boserup's Fund, all non-profit organizations with no rights to approve or disapprove of the manuscript.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.