Premature Coronary Artery Disease Due To Familial Hypercholesterolemia: A Genetic Based Study

Background and aim: premature coronary artery disease (cad) is a major cause of mortality and morbidity in which the increased low-density lipoprotein-cholesterol (ldl-c) level is a major risk factor. familial hypercholesterolemia (fh) is a genetic inherited disorder characterized by high ldl-c, and subsequent premature cad development. the aim of this study is to investigate the sequence alteration of ldlr and pcsk9 genes in patients suffering from premature cad and hypercholesterolemia. methods: 60 individuals with hypercholesterolemia and cardiovascular diseases referred to rajaie cardiovascular, medical, and research center were admitted in this study after signing the informed consent. the genomic dna was extracted using salting out method and the pcr were performed with specific primers which amplify the whole coding exons, exon-intron junctions, and important regions of introns in the ldlr(ng_009060) and pcsk9(ng_009061) genes. all the pcr products were sequenced with the abi 3500 dna sequencer. results: our data revealed that some of the patients have a mutation in ldlr gene. so that at least about 43% of patients suffering from premature cad due to familial hypercholesterolemia. furthermore, these mutations were both novel and reported. conclusion: since controlling the increased low-density lipoprotein-cholesterol (ldl-c) level is the main target for prevention of the cad disease. investigating the genetic causes of hypercholesterolemia help physicians to better understand the root of the disease and to start early drug treatment with lipid-lowering medications in fh patients and their families in order to prevent cardiovascular disease onset.