Upstream Transcription Factor 1 (USF1) allelic variants regulate lipoprotein metabolism in women and USF1 expression in atherosclerotic plaque.

Upstream transcription factor 1 (USF1) allelic variants significantly influence future risk of cardiovascular disease and overall mortality in females. We investigated sex-specific effects of USF1 gene allelic variants on serum indices of lipoprotein metabolism, early markers of asymptomatic atherosclerosis and their changes during six years of follow-up. In addition, we investigated the cis-regulatory role of these USF1 variants in artery wall tissues in Caucasians. In the Cardiovascular Risk in Young Finns Study, 1,608 participants (56% women, aged 31.9 ± 4.9) with lipids and cIMT data were included. For functional study, whole genome mRNA expression profiling was performed in 91 histologically classified atherosclerotic samples. In females, serum total, LDL cholesterol and apoB levels increased gradually according to USF1 rs2516839 genotypes TT < CT < CC and rs1556259 AA < AG < GG as well as according to USF1 H3 (GCCCGG) copy number 0 < 1 < 2. Furthermore, the carriers of minor alleles of rs2516839 (C) and rs1556259 (G) of USF1 gene had decreased USF1 expression in atherosclerotic plaques (P = 0.028 and 0.08, respectively) as compared to non-carriers. The genetic variation in USF1 influence USF1 transcript expression in advanced atherosclerosis and regulates levels and metabolism of circulating apoB and apoB-containing lipoprotein particles in sex-dependent manner, but is not a major determinant of early markers of atherosclerosis.

A Comparison Between the StaRRsed Auto-Compact Erythrocyte Sedimentation Rate Instrument and the Westergren Method.

BACKGROUND: The Westergren method is the golden standard for measuring erythrocyte sedimentation rate (ESR). All ESR methods should agree with the standardized method of the International Council for Standardization in Hematology (ICSH). Citrate samples are commonly used for ESR. This extra sample adds costs and can be inconvenient for the patient. Therefore, some new automated ESR analyzers use EDTA samples, which are available for other hematology measurements. METHODS: We compared ESR measurements with StaRRsed Auto-Compact instrument to the ICSH standardized Westergren method in 200 patient samples. RESULTS: The correlation between methods was fairly good (R(2) = 0.72, y = 1.066x 0.24). However, with ESR results over 11 mm/h there were 55 subjects with a difference of over 30% between methods. CONCLUSIONS: This may have led to different treatment suggestions in 25 cases according to age- and gender-dependent normal values. The difference may be caused by two different anticoagulants used, different measuring times and the correlation equation used. The StaRRsed ESR method should be in better agreement with the Westergren method, which is the golden standard. ESR results have notable impact on patient diagnosis and follow-up. KEYWORDS: ESR; Erythrocyte sedimentation rate; StaRRsed; Westergren method.

The influence of smoking and homocysteine on subclinical atherosclerosis is modified by the connexin37 C1019T polymorphism - The Cardiovascular Risk in Young Finns Study.

BACKGROUND: A polymorphism C1019T on the connexin37 (Cx37) gene has been found to associate with coronary artery disease. There are conflicting results on which allele confers risk, and the possibility of interactions between the polymorphism and risk factors has been raised. In this study, we examined interactions between the Cx37 polymorphism and common risk factors and their associations to early vascular parameters of atherosclerosis: carotid artery intima-media thickness (IMT), and carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD). METHODS: A population of 1440 healthy young adults from the Cardiovascular Risk in Young Finns Study was studied. The subjects were genotyped and their cardiovascular risk factor and ultrasound data gathered in 2001 were used for the statistical analyses. RESULTS: In the whole population, homocysteine in subjects with the TT genotype was found to be associated with higher FMD values (p for interaction 0.038) and remained so in three different adjusted models (p for interaction 0.022-0.038). In women with the CC genotype, smoking was found to be associated with higher FMD values and the smoking-by-genotype interaction remained significant in three adjusted models (p for interaction 0.001-0.041). In women with TT genotype, the effect of smoking was opposite, i.e., FMD values for smokers were lower compared to non-smokers. In men, physical activity interacted with Cx37 on CAC in the CT and TT genotypes (p for interaction 0.011). No significant interactions were found to predict IMT. CONCLUSIONS: The effect of smoking and homocysteine levels on arterial endothelial functions and elasticity were modified by the allelic variation of the Cx37 gene. These data suggest that variation in the connexin gene may modify effects risk factors have on vascular function.

Allelic variants of upstream transcription factor 1 associate with carotid artery intima-media thickness: the Cardiovascular Risk in Young Finns study.

BACKGROUND: Polymorphisms of the upstream transcription factor 1 (USF1) have been associated with familial combined hyperlipidemia and coronary heart disease. The impact of this gene on subclinical atherosclerosis is unknown. Associations of 3 allelic variants of the USF1 gene and their haplotypes with carotid artery intima - media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD) were studied in a population of Finnish healthy young adults. METHODS AND RESULTS: The study population comprised 2,281 individuals participating in the Cardiovascular Risk in Young Finns study. IMT, CAC and FMD values were measured by ultrasound examination. Genotypes were analysed using the 5' nuclease assay. A significant difference in IMT was found for usf1s1 (rs3737787) and usf1s8 (rs2516838) genotypes (p-values 0.046 and 0.021, respectively). Moreover, there was a significant difference between groups in haplotype 1 and haplotype 2 for IMT (p-values 0.011 and 0.028 respectively). In multivariate stepwise linear regression models adjusted by age, sex, body mass index, systolic and diastolic blood pressures, smoking, C-reactive protein, glucose, high- and low-density lipoprotein-cholesterols and triglycerides there were significant associations for the usf1s1 minor genotype AA to predict low IMT (p=0.038) and usf1s8 minor genotype GG to predict high IMT (p=0.003). There was also a significant association for haplotype 2 to predict low IMT in the otherwise similar multivariate model (p=0.006). No associations were found for polymorphisms and CAC, FMD or serum lipids. CONCLUSIONS: The rs2516838 and rs3737787 polymorphisms of USF1 influence the carotid artery IMT, which is a new finding.

Associations between connexin37 gene polymorphism and markers of subclinical atherosclerosis: the Cardiovascular Risk in Young Finns study.

OBJECTIVE: Connexin37 (cx37) C1019T polymorphism has been shown to associate with coronary artery disease in different populations. We investigated whether this polymorphism associates with carotid artery intima-media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD) - i.e., early ultrasound markers of subclinical atherosclerosis - in a clinically healthy population of young Finnish adults. METHODS AND RESULTS: 1440 individuals from the Cardiovascular Risk in Young Finns study were genotyped and studied using cardiovascular risk factor and ultrasound data obtained in 2001. In linear regression models, no significant association between the cx37 polymorphism and carotid IMT, CAC or brachial artery FMD (ANOVA, p=0.159, 0.151 and 0.547), respectively, was found in the whole population or in women and men separately. CONCLUSIONS: The connexin37 C1019T polymorphism is not related with markers of subclinical atherosclerosis in young adults.

Apolipoprotein A-I/C-III/A-IV SstI and apolipoprotein B XbaI polymorphisms and their association with carotid artery intima-media thickness in the Finnish population. The Cardiovascular Risk in Young Finns Study.

Apolipoprotein A-I/C-III/A-IV (apoA-I/C-III/A-IV) SstI and apolipoprotein B (apoB) XbaI polymorphisms have been shown to affect serum low-density lipoprotein (LDL) cholesterol concentrations in a sample of Finnish children. We studied whether these polymorphism are associated with carotid artery intima-media thickness (IMT), a marker of pre-clinical atherosclerosis, measured in the same subjects during their adulthood. A random sub-sample of 214 individuals from the "Cardiovascular Risk in Young Finns" study, for whom genotypes, cardiovascular risk factor data and carotid artery IMT measured in 2001 were available, were studied. Mean carotid IMT values increased according to the apoA-I/C-III/A-IV SstI genotype groups in the order of S1S1 (0.58+/-0.08 mm), S1S2 (0.61+/-0.08 mm), and S2S2 (0.70+/-0.16 mm, p=0.02, ANOVA). In multiple linear regression analysis after adjusting for age, sex and body mass index the mean IMT thickness among the S2 allele carriers was higher (p=0.02) compared to non-carriers. In logistic regression analysis the frequency of S2 allele carriers was higher among the high IMT group compared to the low IMT group (OR=4.02, CI: 1.68-9.61, p=0.002). No significant association between apoB XbaI polymorphism and carotid IMT was found. However, serum total and LDL cholesterol and apoB concentrations were significantly different among apoB genotype groups (p<0.001 for all traits). The apoA-I/C-III/A-IV SstI polymorphism is associated with carotid IMT in young Finns.