Year: 2008
Type: dissertation
Study design: Observational Study
Abstract: Cardiovascular diseases (CVD) are major contributors to morbidity and mortality worldwide.Several interacting environmental, biochemical, and genetic risk factors can increase disease susceptibility.While some of the genes involved in the etiology of CVD are known, many are yet to be discovered.During the last few decades, scientists have searched for these genes with genome-wide linkage and association methods, and with more targeted candidate gene studies.This thesis investigates variation within the upstream transcription factor 1 (USF1) gene locus in relation to CVD risk factors, atherosclerosis, and incidence and prevalence of CVD.This candidate gene was first identified in Finnish families ascertained for familial combined hyperlipidemia, a common dyslipidemia predisposing to coronary heart disease.The gene is a ubiquitously expressed transcription factor regulating expression of several genes from lipid and glucose metabolism, inflammation, and endothelial function.First, we examined association between USF1 variants and several CVD risk factors, such as lipid phenotypes, body composition measures, and metabolic syndrome, in two prospective population cohorts.Our data suggested that USF1 contributes to these CVD risk factors at the population level.Notably, the associations with quantitative measurements were mostly detected among study subjects with CVD or metabolic syndrome, suggesting complex interactions between USF1 effects and the pathophysiological state of an individual.Second, we investigated how variation at the USF1 locus contributes to atherosclerotic lesions of the coronary arteries and abdominal aorta.For this, we used two study samples of middle-aged men with detailed measurements of atherosclerosis obtained in autopsy.USF1 variation significantly associated with areas of several types of lesions, especially with calcification of the arteries.Next, we tested what effect the USF1 risk variants have on sudden cardiac death and incidence of CVD.The atherosclerosis-associated risk variant increased the risk of sudden cardiac death of the same study subjects.Furthermore, USF1 alleles
Source: Työväentutkimus Vuosikirja
Author: Kati Kristiansson
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1910527817