Bad genes, good people, association, linkage, longevity and the preventionof cardiovascular disease

1. Cardiovascular disease, the most common cause of death, is the product o f risk factors such as hypertension, lipid disturbances, diabetes mellitus, left ventricular hypertrophy and nicotine smoking, all of which are influen ced by genetic variance. Thus, genes that influence these factors have a co nsiderable bearing on longevity. 2. Although mortality rates increase exponentially with increasing age, an interesting tendency towards a plateau occurs, suggesting that old individu als are somewhat protected from the propensity to die. This phenomenon is d ifficult to explain. 3. One possibility is a model of repair, in which certain alleles exert a b eneficial 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 sib-pair model, This potentially deleterious effect was counterb alanced by linkage of the D allele to increased heart rate variability, whi ch is potentially a beneficial attribute. Furthermore, in a cohort of the G erman population over age 80 years, it was observed that the D allele occur red at a frequency higher than would be expected. 6. The present study discusses the hypothesis that the ACE gene I/D polymor phism may be a genetic variant with both negative and positive effects.