Predisposition For Cardiovascular Disease Research Articles

The Autosomal Short Tandem Repeat Polymorphisms Are Potentially Associated with Cardiovascular Disease Predisposition in the Latin American Population: A Mini Review.

According to the World Health Organization, cardiovascular diseases (CVDs) are the leading cause of death worldwide across nearly all ethnic groups. Inherited cardiac conditions comprise a wide spectrum of diseases that affect the heart, including abnormal structural features and functional impairments. In Latin America, CVDs are the leading cause of death within the region. Factors such as population aging, unhealthy diet, obesity, smoking, and a sedentary lifestyle have increased the risk of CVD. The Latin American population is characterized by its diverse ethnic composition with varying percentages of each ancestral component (African, European, and Native American ancestry). Short tandem repeats (STRs) are DNA sequences with 2-6 base pair repetitions and constitute ~3% of the human genome. Importantly, significant allele frequency variations exist between different populations. While studies have described that STRs are in noncoding regions of the DNA, increasing evidence suggests that simple sequence repeat variations may be critical for proper gene activity and regulation. Furthermore, several STRs have been identified as potential disease predisposition markers. The present review is aimed at comparing and describing the frequencies of autosomal STR polymorphisms potentially associated with cardiovascular disease predisposition in Latin America compared with other populations.

Giant ankyrin-G regulates cardiac function

Cardiovascular disease (CVD) remains the most common cause of adult morbidity and mortality in developed nations. As a result, predisposition for CVD is increasingly important to understand. Ankyrins are intracellular proteins required for the maintenance of membrane domains. Canonical ankyrin-G (AnkG) has been shown to be vital for normal cardiac function, specifically cardiac excitability, via targeting and regulation of the cardiac voltage-gated sodium channel. Noncanonical (giant) AnkG isoforms play a key role in neuronal membrane biogenesis and excitability, with evidence for human neurologic disease when aberrant. However, the role of giant AnkG in cardiovascular tissue has yet to be explored. Here, we identify giant AnkG in the myocardium and identify that it is enriched in 1-week-old mice. Using a new mouse model lacking giant AnkG expression in myocytes, we identify that young mice displayed a dilated cardiomyopathy phenotype with aberrant electrical conduction and enhanced arrhythmogenicity. Structural and electrical dysfunction occurred at 1 week of age, when giant AnkG was highly expressed and did not appreciably change in adulthood until advanced age. At a cellular level, loss of giant AnkG results in delayed and early afterdepolarizations. However, surprisingly, giant AnkG cKO myocytes display normal INa, but abnormal myocyte contractility, suggesting unique roles of the large isoform in the heart. Finally, transcript analysis provided evidence for unique pathways that may contribute to the structural and electrical findings shown in giant AnkG cKO animals. In summary, we identify a critical role for giant AnkG that adds to the diversity of ankyrin function in the heart.

Prevalence of AdipoQ (+276 G/T) gene polymorphism in Punjabi menopausal women with and without family history of cardiovascular disease

Cardiovascular disease (CVD) is a serious threat in female population particularly after menopause. The prevalence of CVD with associated risk factors in Punjabi population after menopause is rapidly increasing. Adiponectin polymorphism ADIPOQ +276G/T is located in intron 2 which results from G to T substitution. The variants of adiponectin gene are found to be associated with obesity, metabolic syndrome markers and cardiovascular disease. The present study aimed to screen the prevalence of +276 G/T polymorphism of AdipoQ gene in menopausal women of Punjab with and without the family history of CVDGenomic DNA was extracted from intravenous blood for all the participants. Genotyping of +276 G/T polymorphism in the AdipoQ gene was done by polymerase chain reaction (PCR) – based Restriction Fragment Length Polymorphism (RFLP).Prevalence of TT genotype was higher among cases (22.3%) than among controls (4.4%). Statistical significant difference (p<0.05) was observed in the frequency distribution of TT genotype (p=0.020) in cases with positive family h/o CVD. TT genotype also provided significant risk ~9 folds towards CVD predisposition [p=0.001; OR=9.90(3.77-25.99)] in cases with negative family h/o CVD.The present study reveals that prevalence of TT genotype was found to be more in cases as compared to controls and also positive family history of CVD alone does not seem to be a good predictor as individual risk for cardiovascular disease in Punjabi menopausal women.

Cardiovascular safety of non-steroidal anti-inflammatory drugs

The selective cyclooxygenase (COX)-2 inhibitor rofecoxib was withdrawn from the market in 2004 due to cardiovascular toxicity. We have evaluated data on adverse cardiovascular effects caused by COX-2 inhibitors and other non-steroidal anti-inflammatory drugs (NSAIDs) since 2004. Searches in PubMed (2004-2014) identified 243 relevant articles. Following a selection process, 63 articles were reviewed and evaluated in light of Norwegian practice. The results from the studies reviewed are heterogenous. A majority of data indicate that all the selective COX-2 inhibitors, diclofenac and high-dose ibuprofen cause adverse cardiovascular effects to a problematic extent, whereas naproxen consistently exhibits low or no risk. For most NSAIDs high dosage is related to increased risk, and the increase in risk appears to be present from the start of treatment. The effects of length of treatment and predisposition for cardiovascular disease are less clear. Adverse cardiovascular effects is as a group effect that applies to all the NSAIDs studied, except for naproxen and low-dose ibuprofen. The traditional classification of NSAIDs as COX-2 selective and non-selective drugs is unsuited for risk stratification. The current pattern of consumption of NSAIDs in the population does not correspond to our knowledge of the increased risk to which patients are exposed.

Lipoprotein Lipase 1595 C/G and Hepatic Lipase –480 C/T Polymorphisms – Impact on Lipid Profile in Incident Dialysis Patients

Background: Dyslipidemia is a common complication of chronic kidney disease. Lipoprotein lipase (LPL) 1595 C/G and hepatic lipase (HL) –480 C/T single nucleotide polymorphisms (SNPs) influence lipid profile and predisposition for cardiovascular disease in the general population. The present study was undertaken to clarify the impact of the two polymorphisms on lipid parameters and cardiovascular risk in incident dialysis patients. Methods: LPL 1595 C/G and HL –480 C/T SNPs were evaluated in 293 chronic kidney disease patients close to dialysis initiation. Associations with lipid parameters, presence of cardiovascular disease, and survival were assessed. Results: LPL 1595 C/G SNP was associated with significantly lower triglyceride levels [1.55 (1.00–2.20) vs. 1.90 (1.40–2.48) mM; p < 0.01], while HL –480 C/T polymorphism was associated with increased high density lipoprotein cholesterol concentration [1.30 (1.00–1.60) vs. 1.10 (0.90–1.40) mM; p < 0.05]. Neither of the polymorphisms showed any relationship with patient survival. Conclusions: LPL 1595 C/G and HL –480 C/T polymorphisms affect lipid profile in incident dialysis patients.

Genetic variants predisposing to cardiovascular disease

The goal of this review is to provide an update on the most recent and relevant findings in the area of genotype-phenotype associations as well as the relationships between genetic factors and cardiovascular disease risk markers and events. In addition, emphasis will be placed on the methodological problems associated with studying the genetics of complex disorders, specifically cardiovascular diseases. Genes associated with cardiovascular disease predisposition have been examined, including traditional cardiovascular disease candidate genes, such as ACE, AGT, eNOS, PON and MTHFR, new loci that have recently been added to the growing list of cardiovascular disease candidate genes (i.e. MEF2A, ALOX5, LTA, APOM, PDE4D), and genes that have been shown to be at the intersection of several age-related disorders through interaction with one another or with environmental factors (i.e. APOA5, APOE, PPARgamma, LPL and LIPC). During the last year, tremendous effort has been made in elucidating new genes associated with cardiovascular disease predisposition. For the most part, however, major breakthroughs have not been made, primarily due to the poor replication of results among studies, as a consequence of poor experimental design. Nevertheless, we have increased our understanding of the complexity of cardiovascular disease and the relevance of gene-environment interactions as the ultimate drivers of the individual predisposition to the disease. It is essential, therefore, that present and future genetic studies in this area take into consideration the inclusion of high-quality environmental data in the analytical process to test the clinical usefulness of a genetic marker as a risk predictor.

Soluble ICAM-1, VCAM-1 and E-selectin in children from families with high risk of atherosclerosis.

The genetic predisposition for cardiovascular disease seems to play an important role in atherogenesis. Atherosclerosis, which can be clinically asymptomatic for many years, begins early in life. Therefore finding markers of early atherosclerotic process would be of great importance for screening and early treatment of these children. As the result of endothelial dysfunction, the adhesion molecules (VCAM-1, ICAM-1, ELAM) are overexpressed. These molecules are shed from the surface and can be measured, as soluble forms in serum. Therefore they can be regarded as early markers of atherosclerosis. The aim of the study was to measure the serum levels of soluble adhesion molecules ELAM, ICAM-1, VCAM-1 and plasma lipid profile--total (TC), LDL (LDL-C) and HDL-cholesterol (HDL-C) and triglycerides (TG) in children from families of high risk for cardiovascular diseases. Forty-eight children were studied, 24 children from high risk families, according to NCEP definition: one or two parents had clinical manifestation of cardiovascular disease before the age of 65 years (mother) or 55 years (father). Twenty-four healthy children without familial history of cardiovascular disease were used as the control. Children of either group did not have any metabolic diseases. The concentration of sELAM, sICAM-1 and sVCAM-1 were assessed using ELISA kits. Soluble ICAM-1 level was significantly higher in high risk group in comparison to control (p<0.02). The soluble VCAM-1 and ELAM levels did not differ significantly between the groups. There were no changes in total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides between the groups. In normolipidemic children from families with high risk for atherosclerosis the soluble ICAM-1 levels are significantly higher as compared to control.

The genetic revolution in artificial reproduction: a view of the future.

With the completion of the human genome project, micro-array technology offers the potential to open up a whole new vista in assisted reproduction. In the next 10-20 years we will be able to screen each human embryo for all numerical chromosomal abnormalities as well as many genetic diseases. Micro-array analysis may permit the screening of multiple alleles for monogenetic diseases and polygenic diseases, including diabetes, hypertension and schizophrenia. In the near future, it may be possible to assess an individual's genetic predisposition for cardiovascular disease, all types of cancer and infectious diseases. In the distant future, it may even be possible to screen for any genetic trait, e.g. stature, baldness, obesity, hair colour, skin colour or even IQ. Although it is still uncertain what molecular genetic tools may be available, we can be sure that some of these trends will have major consequences on the future of assisted reproduction and society at large.