We also identify SORT1 and CELSR2 as candidate susceptibility genes for a locus recently associated with coronary artery disease and plasma low-density lipoprotein cholesterol levels in the process.
Genetic variation at chromosome 1p13.3 affects sortilin mRNA expression, cellular LDL-uptake and serum LDL levels which translates to the risk of coronary artery disease.
Compelling evidence linking the SORT1 gene to both LDL cholesterol (LDL-C) levels and the risk of coronary artery disease emerged from the data, prompting the search for the molecules and mechanisms responsible for this association.
Examples include a role for NO signaling in myocardial repolarization and sudden cardiac death and a role for the protein sortilin in lipid metabolism and coronary artery disease.
The genetic loci for ATP-binding cassette transporters G5 and G8, Niemann-Pick C1-Like protein 1, sortilin-1, ABO blood-group glycosyltransferases, myosin regulatory light chain-interacting protein and cholesterol 7α-hydroxylase have all consistently been associated with LDL cholesterol levels and/or coronary artery disease in GWAS.
Effect of SORT1, APOB and APOE polymorphisms on LDL-C and coronary heart disease in Pakistani subjects and their comparison with Northwick Park Heart Study II.
Increased sortilin and its independent effect on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in statin-naive patients with coronary artery disease.