The genetics of cardiovascular disease

Delles, Christian; McBride, Martin W.; Padmanabhan, Sandosh; Dominiczak, Anna F.

doi:10.1016/j.tem.2008.07.010

Cited by 13 publications

(12 citation statements)

References 71 publications

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“…Several genes were found to modulate susceptibility to CVD including more than 100 loci [33, 34]. The prevalence of such risk factors among studied population will be a matter of our future research.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Cardiovascular Risk Factors Among University Students: The Gender Factor

et al. 2012

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BackgroundEvidence indicates that the pathophysiological process of cardiovascular (CV) disease begins at early age, though the manifestations of the disease do not appear until middle age adulthood. Risk factors for CV disease, particularly lipoprotein profiles, are affected by physiological abnormalities, and lifestyle related issues. To evaluate prevalence of CV diseases risk factors among university students and to investigate relation between number of risk factors and body anthropometric, hematological and biochemical indices parameters.MethodsIn this cross sectional study, 348 students were randomly recruited. Blood glucose, cholesterol profile (total, HDL, and LDL cholesterol), and triglyceride were measured using standard protocols. Physical activity (PA) level was assessed using the short-form Arabic version of the International Physical Activity Questionnaires (IPAQ).ResultsThe most commonly encountered CV disease risk factor was low levels of HDL-C, followed by physical inactivity, high levels TG, and obese BMI. When stratified by gender, females were less likely to have low HDL-C, and high TG, whereas, males were more likely to have overweight or obese BMI (P < 0.001). About 49% of the participants had at least one CV disease risk factor, where as the prevalence of having one, two and three or more CV disease risk factors were 35.7%, 9.3% and 4%, respectively. Additionally, the number of CV disease risk factors showed strong positive correlation with increases in body fat and bone percentages, glucose, total cholesterol, TG, LDL-C, BMI, and WHR (range of R2: 0.17 to 0.603). On the other hand, physical activity, percentages of body water and muscle, HDL-C showed inverse strong correlation with cardiovascular risk factors (range of R2: -0.239 to -0.412).ConclusionsResults indicate the high prevalence of CV disease risk factors among university students, and stress the need for early intervention programs to counteract these risks.

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Section: Discussionmentioning

confidence: 99%

Assessment of Cardiovascular Risk Factors Among University Students: The Gender Factor

et al. 2012

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“…Genetic and epigenetic changes have been shown to influence individual-level responses to ambient pollution for a wide variety of cardiovascular effects [9-11]. Studies have shown that polymorphisms in genes related to oxidative stress may alter susceptibility to air pollution as measured by biomarkers of endothelial and vascular function [12-16].…”

Section: Introductionmentioning

confidence: 99%

Ambient pollutants, polymorphisms associated with microRNA processing and adhesion molecules: the Normative Aging Study

et al. 2011

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BackgroundParticulate air pollution has been associated with cardiovascular morbidity and mortality, but it remains unclear which time windows and pollutant sources are most critical. MicroRNA (miRNA) is thought to be involved in cardiovascular regulation. However, little is known about whether polymorphisms in genes that process microRNAs influence response to pollutant exposure. We hypothesized that averaging times longer than routinely measured one or two day moving averages are associated with higher soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) levels, and that stationary and mobile sources contribute differently to these effects. We also investigated whether single nucleotide polymorphisms (SNPs) in miRNA-processing genes modify these associations.MethodssICAM-1 and sVCAM-1 were measured from 1999-2008 and matched to air pollution monitoring for fine particulate matter (PM2.5) black carbon, and sulfates (SO42-). We selected 17 SNPs in five miRNA-processing genes. Mixed-effects models were used to assess effects of pollutants, SNPs, and interactions under recessive inheritance models using repeated measures.Results723 participants with 1652 observations and 1-5 visits were included in our analyses for black carbon and PM2.5. Sulfate data was available for 672 participants with 1390 observations. An interquartile range change in seven day moving average of PM2.5 (4.27 μg/m3) was associated with 3.1% (95%CI: 1.6, 4.6) and 2.5% (95%CI: 0.6, 4.5) higher sICAM-1 and sVCAM-1. Interquartile range changes in sulfates (1.39 μg/m3) were associated with 1.4% higher (95%CI: 0.04, 2.7) and 1.6% (95%CI: -0.4, 3.7) higher sICAM-1 and sVCAM-1 respectively. No significant associations were observed for black carbon. In interaction models with PM2.5, both sICAM-1 and sVCAM-1 levels were lower in rs1062923 homozygous carriers. These interactions remained significant after multiple comparisons adjustment.ConclusionsPM2.5 seven day moving averages are associated with higher sICAM-1 and sVCAM-1 levels. SO4-2 seven day moving averages are associated with higher sICAM-1 and a suggestive association was observed with sVCAM-1 in aging men. SNPs in miRNA-processing genes may modify associations between ambient pollution and sICAM-1 and sVCAM-1, which are correlates of atherosclerosis and cardiovascular disease.

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“…), which is considered a number one cause of premature death and disability. Although CVD has been shown to have significant heritability, pinpointing of the genes and variants associated with the elevated risk to the disease has been challenging [1,2]. The focus has slowly switched from DNA variants located in genic regions causing direct changes in the encoded protein to the regulatory variants affecting gene expression.…”

Section: Introductionmentioning

confidence: 99%

Hypervariable intronic region in NCX1 is enriched in short insertion-deletion polymorphisms and showed association with cardiovascular traits

et al. 2010

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BackgroundConserved non-coding regions (CNR) have been shown to harbor gene expression regulatory elements. Genetic variations in these regions may potentially contribute to complex disease susceptibility.MethodsWe targeted CNRs of cardiovascular disease (CVD) candidate gene, Na(+)-Ca(2+) exchanger (NCX1) with polymorphism screening among CVD patients (n = 46) using DHPLC technology. The flanking region (348 bp) of the 14 bp indel in intron 2 was further genotyped by DGGE assay in two Eastern-European CVD samples: essential hypertension (HYPEST; 470 cases, 652 controls) and coronary artery disease, CAD (CADCZ; 257 cases, controls 413). Genotype-phenotype associations were tested by regression analysis implemented in PLINK. Alignments of primate sequences were performed by ClustalW2.ResultsNine of the identified NCX1 variants were either singletons or targeted by commercial platforms. The 14 bp intronic indel (rs11274804) was represented with substantial frequency in HYPEST (6.82%) and CADCZ (14.58%). Genotyping in Eastern-Europeans (n = 1792) revealed hypervariable nature of this locus, represented by seven alternative alleles. The alignments of human-chimpanzee-macaque sequences showed that the major human variant (allele frequency 90.45%) was actually a human-specific deletion compared to other primates. In humans, this deletion was surrounded by other short (5-43 bp) deletion variants and a duplication (40 bp) polymorphism possessing overlapping breakpoints. This indicates a potential indel hotspot, triggered by the initial deletion in human lineage. An association was detected between the carrier status of 14 bp indel ancestral allele and CAD (P = 0.0016, OR = 2.02; Bonferroni significance level alpha = 0.0045), but not with hypertension. The risk for the CAD development was even higher among the patients additionally diagnosed with metabolic syndrome (P = 0.0014, OR = 2.34). Consistent with the effect on metabolic processes, suggestive evidence for the association with heart rate, serum triglyceride and LDL levels was detected (P = 0.04).ConclusionsCompared to SNPs targeted by large number of locus-specific and genome-wide assays, considerably less attention has been paid to short indel variants in the human genome. The data of genome dynamics, mutation rate and population genetics of short indels, as well as their impact on gene expressional profile and human disease susceptibility is limited. The characterization of NCX1 intronic hypervariable non-coding region enriched in human-specific indel variants contributes to this gap of knowledge.

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The genetics of cardiovascular disease

Cited by 13 publications

References 71 publications

Assessment of Cardiovascular Risk Factors Among University Students: The Gender Factor

Assessment of Cardiovascular Risk Factors Among University Students: The Gender Factor

Ambient pollutants, polymorphisms associated with microRNA processing and adhesion molecules: the Normative Aging Study

Hypervariable intronic region in NCX1 is enriched in short insertion-deletion polymorphisms and showed association with cardiovascular traits

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