Bad Genes, Good People, Association, Linkage, Longevity and the Prevention of Cardiovascular Disease

Cardiovascular disease, the most common cause of death, is the product of risk factors such as hypertension, lipid disturbances, diabetes mellitus, left ventricular hypertrophy and nicotine smoking, all of which are influenced by genetic variance. Thus, genes that influence these factors have a considerable bearing on longevity. 2. Although mortality rates increase exponentially with increasing age, an interesting tendency towards a plateau occurs, suggesting that old individuals are somewhat protected from the propensity to die. This phenomenon is difficult to explain. 3. One possibility is a model of repair, in which certain alleles exert a beneficial influence at an advanced age. 4. An alternative explanation might be a mutation that exerts both negative and positive effects. 5. The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene exerts was observed to have an effect on heart size. The D allele was linked to a greater heart size, compared with the I allele in a modified sibpair model. This potentially deleterious effect was counter-balanced by linkage of the D allele to increased heart rate variability, which is potentially a beneficial attribute. Furthermore, in a cohort of the German population over age 80 years, it was observed that the D allele occurred at a frequency higher than would be expected. 6. The present study discusses the hypothesis that the ACE gene I/D polymorphism may be a genetic variant with both negative and positive effects.