Year: 2007
Type: article
Study design: Observational Study
Abstract: Cardiovascular diseases (CVD) are a major cause of death and disability in Western countries and a growing health problem in the developing world.The genetic component of both coronary heart disease (CHD) and ischemic stroke events has been established in twin studies, and the traits predisposing to CVD, such as hypertension, dyslipidemias, obesity, diabetes, and smoking behavior, are all partly hereditary.This thesis aimed to clarify the genetic background of CVD at a population level using large Nordic population cohorts and a candidate gene approach.The first study concentrated on the allelic diversity of the thrombomodulin (THBD) gene in two Finnish cohorts, FINRISK-92 and FINRISK-97.The results from this study implied that THBD variants do not substantially contribute to CVD risk.In the second study, three other candidate genes were added to the analyses.The study investigated the epistatic effects of coagulation factor V (F5), intercellular adhesion molecuce -1 (ICAM1), protein C (PROC), and THBD in the same FINRISK cohorts.The results were encouraging; we were able to identify several single SNPs and SNP combinations associating with CVD and mortality.Interestingly, THBD variants appeared in the associating SNP combinations despite the negative results from Study I, suggesting that THBD contributes to CVD through gene-gene interactions.In the third study, upstream transcription factor -1 (USF1) was analyzed in a cohort of Swedish men.USF1 was associated with metabolic syndrome, characterized by accumulation of different CVD risk factors.A putative protective and a putative risk variant were identified.A direct association with CVD was not observed.The longitudinal nature of the study also clarified the effect of USF1 variants on CVD risk factors followed in four examinations throughout adulthood.The three studies provided valuable information on the study of complex traits, highlighting the use of large study samples, the importance of replication, and the full coverage of the major allelic variants of the target genes to assure reliable findings.
Author: Kirsi Auro
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1077033501, G6091493096
OpenAlex ID: W1163213122