Colombia is one of the countries where human aging is expected to have a greater impact in the world; the life expectancy in 1930 in Colombia was 40.7 years and is estimated to be 74 years in 2015 (6,19). As opposed to de- veloped countries, Colombian population has particular and differential genetic features (the population living in Bogo- ta´ has an admixture of Caucasian and Native American ge- netic backgrounds) (20) and environmental characteristics (such as education, diet, occupation, health services use, among others). Therefore, an analysis of candidate genetic polymorphisms for human longevity in the Colombian pop- ulation is of interest. In the current work we have not found significant differences in the frequency of APOE polymor- phism (allele or genotype) between different age groups in a large Colombian sample (538 subjects). We found a signif- icant decrease in the frequency of the ACE DD genotype in the older group sample compared to the younger sample (24

Discussion

Although the exploration of genetic factors involved in the mechanisms of human aging through association studies have received increasing support (2,7), the majority of genetic association studies of human longevity have been performed in North America, Europe and Asia. It has been proposed that the expression of human phenotypes of med-

Table 1. Allele and genotype frequencies for APOE polymorphism in different age groups in Colombia

50.0 40.0 ACE I/II 30.0 ACE I/D ACE D/D 20.0 10.0 0.0 1 2 Age Groups )%( seicneuqerF epytoneG

40 years (18–65 years) 77 years (66–106 years) Mean age (range) n % n % Genotype 22 2 0.7 1 0.4 23 23 8.2 18 7.0 24 4 1.4 0 0.0 33 208 74.0 194 75.5 34 42 14.9 40 15.6 44 2 0.7 4 1.6 Total 281 100.0 257 100.0 Alelle n % n % 2 31 5.5 20 3.9 3 481 85.6 446 86.8 4 50 8.9 48 9.3 Total 562 100.0 514 100.0

Figure 1. Allele and genotype frequencies for ACE polymorphism in dif- ferent age groups in Colombia (group 1: mean age 5 45 years, group 2: mean age 5 77 years).

vs. 16%). This decrease in ACE DD genotype as well as in the D allele was more evident in women. A lack of statisti- cal power due to the smaller size of the subsample of men may be an explanation for our failure to detect an associa- tion of ACE DD and longevity in male subjects in this sam- ple. It is important to highlight that sex-dependent genetic associations with human longevity have been reported with several polymorphisms (7). Preliminary data from an ongo- ing analysis of selected demographic and environmental variables for a subset of the sample of older subjects (206 individuals) showed higher values for BMI and serum total cholesterol and lower rates of smoking in women (unpub- lished results). Consistent with these demographic variables and a non-lineal effect of specific polymorphisms on human longevity, there is the possibility that other unknown envi- ronmental and genetic variables accounted for the earlier death of men (in comparison to women) in this sample, and that the interaction of specific genetic variants (ACE DD genotype) with some female-specific environmental characteristics found in this population (higher serum cho- lesterol, for example) may account for a earlier death of ACE DD carriers and the decreased frequency of this geno- type seen in older women in this study. The mean age of the older subjects (77 years) corresponded to |30 years more than the estimated life expectancy of their birth year cohort (40.7 years) (19).

Previously, we found a higly significant association in our population between several SNPs in the APOE gene and Alzheimer‘s disease (16,37), but not with ACE or A2M genes (17).

A future analysis in the present population of other promising candidate genes for human longevity (MTP, WRN, among others) (2,38), together with the analysis of additional SNPs in the ACE I gene having a possible func- tional effect (39) and analysis of ACE serum levels (26) in older subjects and their younger relatives (40) will be important.

Acknowledgments

This work was supported by a grant from DIB-UNAL (822002) and COLCIENCIAS (11010416404). The authors thank Dr. Jorge Lo´pez and members of Beneficencia of Cundinamarca for their help in recruiting older subjects.

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