Here we review all the experiments that led to the identification of the new pathway connecting sortilin with plasma LDL levels and risk of myocardial infarction.
Our results establish two SNPs, rs17465637 in MIA3 and rs599839 near SORT1 as significant risk factors for MI in the American Genebank Caucasian population.
Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene).
An accompanying study in Nature identified SORT1 as the causal gene at the 1p13 locus and showed that increased expression of sortilin-1 protein in liver was associated with lower LDL-C levels and a reduced risk of myocardial infarction.
Association of the single nucleotide polymorphism rs599839 in the vicinity of the sortilin 1 gene with LDL and triglyceride metabolism, coronary heart disease and myocardial infarction. The Ludwigshafen Risk and Cardiovascular Health Study.