Browsing by discipline "Molecular neurology"

Background: Atherosclerosis is a common pathological process in arteries causing significant morbidity and mortality due to stroke and myocardial infarction. The progression of atherosclerosis is affected by both genes and external factors that interactively initiate and advance the pathological cascade. Heme oxygenase 1 (HO1) is a protein that degrades toxic heme and thereby plays a role in maintaining normal vascular function. The expression of the heme oxygenase 1 gene (HMOX1) is affected by a (GT)n polymorphism in its promoter area; short (GT)n alleles associate with higher HO1 expression in cell culture studies and are hypothesized to protect vessel wall from hemi-related oxidative damage. Objective: Our research group has previously found that patients that have suffered stroke due to atherosclerotic carotid stenosis show high expression of HMOX1 in their carotid plaques (CPs). The aim of this thesis was to investigate whether this finding is explained by the HMOX1 (GT)n promoter polymorphism, i.e. if the promoter polymorphism is associated to symptomatic carotid disease. Methods: HMOX1 promoter (GT)n polymorphism was genotyped in carotid stenosis patients (HeCES n=92) and population controls (Health 2000 Survey, n=964). HMOX1 mRNA and protein levels were measured from CPs by qRT-PCR and ELISA, respectively. Results: HMOX1 promoter (GT)n alleles in the Finnish population ranged between 20 and 40 repeats, where (GT)30 was the most common allele with a population frequency of 46.6%. When comparing carotid stenosis patients to controls, statistically significant association between a lack of short alleles (< (GT)30) and symptomatic carotid disease was not found (p=0.214). Whereas, carotid stenosis patients with an ulcerative plaque lacked significantly more often a short allele at the HMOX1 promoter variant (p=0.006). However, we did not find correlation between promoter genotypes and HMOX1 mRNA or protein levels in the CPs. Conclusions: Our results support the protective role of short HMOX1 promoter (GT)n variants against symptomatic carotid artery disease (CaD).