Genetics of cardiovascular disease: a candidate gene study of USF1

摘要: Cardiovascular diseases (CVD) are major contributors to morbidity and mortality worldwide. Several interacting environmental, biochemical, genetic risk factors can increase disease susceptibility. While some of the genes involved in etiology CVD known, many yet be discovered. During last few decades, scientists have searched for these with genome-wide linkage association methods, more targeted candidate gene studies. This thesis investigates variation within upstream transcription factor 1 (USF1) locus relation factors, atherosclerosis, incidence prevalence CVD. was first identified Finnish families ascertained familial combined hyperlipidemia, a common dyslipidemia predisposing coronary heart disease. The is ubiquitously expressed regulating expression several from lipid glucose metabolism, inflammation, endothelial function. First, we examined between USF1 variants such as phenotypes, body composition measures, metabolic syndrome, two prospective population cohorts. Our data suggested that contributes at level. Notably, associations quantitative measurements were mostly detected among study subjects or suggesting complex interactions effects pathophysiological state an individual. Second, investigated how atherosclerotic lesions arteries abdominal aorta. For this, used samples middle-aged men detailed atherosclerosis obtained autopsy. significantly associated areas types lesions, especially calcification arteries. Next, tested what effect on sudden cardiac death atherosclerosis-associated variant increased same subjects. Furthermore, alleles follow-up These prominent women, sex-specific effect, which has also been subsequent Finally, low-yield DNA cohort needed whole-genome amplified (WGA) prior genotyping, evaluated whether produced WGA genotypes good quality. Although giving genotype discrepancies could not before genotyping standard laboratory quality control our results enhanced time identify samples. In addition, combining reactions into one pooled sample markedly reduced number showing them. conclusion, seems role Additional studies warranted functional other environmental factors. study, low yield samples, benefit whole genome amplification genotyping. Careful procedures are, however,