Introduction

This chapter summarizes the large volume of relatively recent work devoted to finding genetic polymorphisms that are linked to the development of cardiovascular disease (CVD) and acute coronary syndromes (ACS). These markers might become part of a panel of laboratory tests and clinical indicators that will be used for predicting future CVD risk. The medical literature is exploding in the last 10 yr with genotype-disease association studies. As such, the criteria for establishing high-quality genetic association studies are now needed and have been opined by some. One such list is shown in Table 1 (1). With specific regard to polymorphic studies with CVD, Jones and Montgomery described necessary additional steps (2) (Table 2). Candidate polymorphisms should be directed against genes that produce products known to be involved in the pathophysiology of cardiac diseases. In the case of ACS, this would include (but not be limited to) genes that regulate inflammation, thrombosis, platelet function, lipoproteins, and other markers of atherosclerosis. In the case of congestive heart failure (CHF), this would include genes that regulate the renin-angiotensin-aldosterone axis, natriuretic peptides, and adrenoreceptors. Having identified polymorphisms in candidate genes, it would be desirable to show that the variants produce different concentrations and/or functional capabilities of the expressed protein. This can demonstrated by an in vitro cell culture model or in human studies in which the concentration of the protein in the variant is compared against that found in the wild type. Having fulfilled one or both of these criteria, a clinical study can be conducted that compares the incidence the the polymorphisms in diseased and carefully selected control populations. The pheno-type of the diseased population should be tightly controlled. It is not appropriate to combine ischemic cardiomyopathy patients with CHF patients who have a valvular etiology. It is also important to identify and exclude confounding variables such as the use of cardiac medications that modify the expression and concentration of the target protein. As most studies to date have only shown a modest relative risk ratio, the number of subjects enrolled should be sufficiently powered to detect a small but significant difference. Meta-analyses are important to increase the enrollments necessary to achieve the discriminatory power.

Table 3 lists some of the major single-nucleotide polymorphisms (SNPS), variable number of tandem repeats (VNTRs) and insertion/deletion mutations genes that are discussed in this chapter. The identification of specific and relevant genotypes might ultimately have an impact beyond risk stratification. The future emphasis of polymorphisms in cardiac disease will be focused on pharmacogenomics (i.e., the determination of genotypes prior to the selection of drugs for treatment). In the future, it might be necessary to document a certain genotype for the proper selection of statins for primary CVDs, drugs for hypertension, angiotensin-converting enzyme and P-blockers for heart failure, or glycoprotein Ilb/IIIa inhibitors in ACS. Although this field is in its infancy, CVDs might be one area that would benefit greatly from this technology.

Your Heart and Nutrition

Your Heart and Nutrition

Prevention is better than a cure. Learn how to cherish your heart by taking the necessary means to keep it pumping healthily and steadily through your life.

Get My Free Ebook


Post a comment