Objective-A rare mutation in low-density lipoprotein receptor-related protein 6 gene (LRP6) was identified as the primary molecular defect underlying monogenic form of coronary artery disease. We hypothesized that common variants in LRP6 could predispose subjects to elevated LDL-cholesterol (LDL-C). Methods and Results-Twelve common (minor allele frequency Ն0.1) single nucleotide polymorphisms in LRP6 were genotyped in 703 individuals from 213 Polish pedigrees (Silesian Cardiovascular Study families). The family-based analysis revealed that the minor allele of rs10845493 clustered with elevated LDL-C in offspring more frequently than expected by chance (Pϭ0.0053). The quantitative analysis restricted to subjects free of lipid-lowering treatment confirmed the association between rs10845493 and age-, sex-, and BMI-adjusted circulating levels of LDL-C in families as well as 2 additional populations Ϫ 218 unrelated subjects from Silesian Cardiovascular Study replication panel and 1138 individuals from Young Men Cardiovascular Association cohort (Pϭ0. 0268, Pϭ0.0476, and Pϭ0.0472, respectively). In the inverse variance weighted meta-analysis of the 3 populations each extra minor allele copy of rs10845493 was associated with 0.14 mmol/L increase in age-, sex-, and BMI-adjusted LDL-C (SEϭ0.05, Pϭ0.0038). Key Words: gene Ⅲ genetics Ⅲ LDL-cholesterol Ⅲ lipids Ⅲ association L ow-density lipoprotein cholesterol (LDL-C) is the most powerful independent predictor of death from cardiovascular disease. 1 The association between circulating concentrations of LDL-C and death from coronary artery disease (CAD) is continuous across a wide spectrum of cardiovascular risk. 2 Similarly, there is a linear relationship between LDL-C lowering and the attenuation in risk of death from cardiovascular disease-each 1%-reduction in LDL-C plasma levels correlates with a 1%-decrease in CAD mortality. 3 LDL-C shows Ͼ50% heritability 4 and correlates with familial predisposition to CAD even in young apparently healthy subjects. [5][6] The recent genome-wide association scans (GWAs) and the subsequent replication studies have identified several common polymorphic variants with very significant impact on LDL-C levels. 7-8 However, the collective contribution of the variants identified through GWAs to the overall interindividual variation in LDL-C is modest and does not fully explain its entire heritability. 8 Clearly, additional strategies are needed to identify the remaining genetic contributors to human hyperlipidemia. One of the potential approaches to uncover these loci is a systematic analysis of common alleles in genes responsible for rare monogenic syndromes of human cardiovascular disorders. Using this conceptual strategy in relation to genes underlying monogenic forms of hypertension and hypotension, we have recently revealed that common alleles within the locus responsible for type 2 Bartter syndrome (KCNJ1) are associated with blood pressure in the general population. 9 Lowdensity lipoprotein receptor-related protein 6 gene (LRP6)-re...
1. Circulating EPC count at rest is comparable between subjects with premature atherosclerosis and healthy volunteers. 2. A single bout of physical exercise causes a significant increase in circulating EPC count in both groups, but the dynamics of exercise-induced EPC mobilisation is different, with delayed exercise-induced EPC mobilisation in subjects with premature CAD. 3. The extent of atherosclerotic coronary lesions does not influence circulating EPC count at rest.
A b s t r a c tBackground: Cardiovascular disease (CVD) is one of the major health problems of the modern societies. Socioeconomic status (SES) is an important predictor of CVD and its risk factors.
Aim:To examine whether SES is related to an increased cardiovascular (CV) risk in the population of southwestern Poland.
Methods:The study population comprised 2027 subjects, including 929 (45.8%) men and 1098 (54.2%) women participating in the WOBASZ study. From this population, we selected a subgroup of 1821 subjects free from CVD, including 816 men and 1005 women, all with defined SES. Their CV risk was estimated using the SCORE risk algorithm and an analysis of the relationship between SES indicators and the SCORE risk was performed.
Results:We found a negative correlation between the SCORE risk and SES (p = 0.0005). In the overall study group and among participating women, the SCORE risk was significantly lower among subjects with high SES (SES score > 12). This relation was also noted in men and women aged 30-39 years (p = 0.02), women aged 30-39 years (p = 0.0001) and 40-49 years (p = 0.04), and in men aged 70-74 years (p = 0.046). With an increase in SES, the proportion of high CVD risk subjects decreased significantly in the overall study population and in those aged 30-39 years (p = 0.01). Similar relations were observed in women in the entire age range and those aged 30-39 years (p = 0.01). We found that SES had a significant effect on the rate of high CVD risk in all study subgroups aged 30-39 years (odds ratio 0.57, 95% CI 0.39-0.85, p = 0.005 in men and women overall; odds ratio: 0.6, 95% CI 0.37-0.99, p = 0.045 in men; and odds ratio: 0.4, 95% CI 0.16-0.99, p = 0.01 in women) Conclusions: Socioeconomic status was found to be a predictor of high CVD mortality risk in men and women aged 30-39 years.
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