Association of single nucleotide polymorphisms in the LPA gene region with serum Lp(a) levels and myocardial infarction

Elevated serum Lp(a) levels are a risk factor for atherosclerosis and myocardial infarction. Lp(a) serum levels are highly heritable, and to a great extend determined by the LPA locus on chromosome 6q27. Polymorphisms influencing the Lp(a) levels have already been identified, but a proportion of the variance in Lp(a) levels remains to be explained. In this investigation different methods were used to explore the influence of SNP markers located in the LPA gene region on Lp(a) levels. The methods comprised a pooling strategy that made use of data from a previous linkage analysis, and served as a screening tool for probably relevant SNP markers. For several SNP markers an association with serum Lp(a) levels could be shown. The identified SNP markers were genotyped in individuals of a large family sample and findings were replicated for all investigated markers. In a third step, a sample of the general population was investigated to underline the robustness of findings. Furthermore, for SNP markers showning a strong association with Lp(a) levels, the association with myocardial infarction (MI) and coronary artery disease was investigated. Particularly one SNP marker in the LPA gene could be identified. This marker (rs11751605) showed a strong influence on Lp(a) levels in multiple populations and is significantly associated with both familial and incidental MI. Moreover, it contributes to the evidence of linkage to the Lp(a) locus on chromosome 6q27. Association with Lp(a) levels and with CAD could be replicated for a SNP marker (rs3798220) recently described in the literature. Furthermore data from a genome-wide association analysis using 500,000 SNP markers were analyzed. The results provide the basis for the identification of factors (apart from markers in LPA gene region) modulating Lp(a) levels.