individuals (48 males and 48 females). No significant differences were observed in allele or genotype frequencies between the old and young populations at this locus (data not shown). 

The study investigated the association between genes associated with cardiovascular risk and longevity, specifically the apo E:apo C-I, angiotensin converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR) genes. The study compared allele and genotype frequencies at polymorphic loci associated with these genes in elderly individuals aged 84 years and older with a younger population aged 17 years or less. The results showed that MTHFR allele and genotype frequencies were similar in both the elderly and young populations. Apo C-I allele and genotype frequencies were significantly different in elderly women compared to the younger sample, but no difference was observed in elderly men. There was a difference between genotypes in elderly women and the young sample at the neighbouring apo E gene, but this did not retain significance when adjusted for values expected from the allele frequencies on the basis of Hardy-Weinberg equilibrium. The ACE I:I genotype was depleted in elderly men but not women, and significant differences were observed between ACE genotypes in elderly men and women. 

The study suggests that genetic factors may affect human survival, with greater concordance for age of death observed in monozygotic compared to dizygotic twins. While many genetic influences affect specific diseases contributing to premature mortality, it is possible that genetic variables have broader biological effects. The study highlights the need for clarification of the overall effect of a genotype on survival to consider therapies targeting specific genetic variants.individuals. The allele associated with the presence of the restriction site was designated as 2. The frequencies of the 1:1, 1:2 and 2:2 genotypes at this locus were as follows for elderly men: 0.18, 0.52, 0.30; elderly women: 0.26, 0.54, 0.20; and young population: 0.28, 0.52, 0.20, respectively. No significant differences were observed for these allele or genotype frequencies when comparing the young population to the total elderly population, the old women, or the old men.

3.1. Apo E and Apo C-I

The apo E allele distributions of the young population were not significantly different from either the total elderly population or the elderly men or women (Table 1). Analysis of apo E genotypes was restricted to E3:3, E3:4 and E2:3 since the other genotypes were too rare to allow expected values of 5 or more in the contingency tables (Table 1). No significant difference was found when comparing the total elderly sample or the elderly men to the young sample. However, the genotype frequencies of the elderly women differed from those of the young sample (χ2=7.49, 2 d.f., P<0.05). Since apo E allele frequencies were not different in the elderly women compared to the young sample, we also derived genotype frequencies in the young group from their allele frequencies on the basis of expectations according to Hardy-Weinberg equilibrium. This procedure was used under the assumption that no selection for apo E had occurred in the young group and that the genotype frequencies derived from the allele frequencies in the young group may be more representative than the observed genotypes, given the random variation of six genotypes that would be expected to occur in a sample of 200. These genotype frequencies were not significantly different from the observed genotypes in the elderly women.

Genotype Apo E, apo C-I, ACE and MTHFR genotypes were determined as described by Hixson and Vernier [14], Nillesen et al. [15], Rigat et al. [16] and Frosst et al. [17], respectively. Observed allele and genotype frequencies were compared in the different groups using χ2 tests. Differences in genotype frequencies between groups were also analyzed by a likelihood ratio test, in which the genotype frequencies in the young were constrained to be in Hardy-Weinberg equilibrium and compared to the observed allele frequencies in the elderly men and women. Relative risks (odds ratios) and confidence limits for each of the polymorphisms were calculated using standard methods [18]. Since apo C-I and apo E are less than 10 kb apart, apo C-I genotype, and allele frequencies can be used to confirm associations at the apo E locus (Table 2). There were no significant differences in either allele or genotype frequency distributions in the elderly men or the total elderly sample compared to the total young sample. However, both allele and genotype frequencies were significantly different in the elderly women compared to the young sample (χ2=4.49, 1 d.f., P<0.05; and χ2=6.16, 2 d.f., P<0.05, respectively). The difference in genotype frequencies becomes non-significant if the frequencies in the young sample are constrained to be in Hardy-Weinberg equilibrium and compared to the observed genotype frequencies in the elderly women (χ2=4.95, 2 d.f., P>0.08).

3.2. ACE