X2- chi-square; CI - confidence interval

Surprisingly, however, in our results, individuals with the E3E4 genotype had a significantly higher mean age than E3E3 individuals did. Differences in the ApoE frequencies and longevity strongly suggest that the relations between certain genotypes and longevity are also influenced by other variables, such as environmental factors and the inte- raction with other genetic factors. This variation could be responsible for the difficulty in defining a biological and cli- nical profile strongly correlated with the risk factors for car- diovascular diseases at advanced ages (> 80 years). There- fore, we believe that this may have contributed to the result obtained.

showed a higher mortality in the group of individuals with low blood pressure (both systolic and diastolic) than that in the group of individuals with higher-than-expected blood pressure 35. This result was later confirmed in similar studies, including the Framingham Study, in which the participants ‡ were divided into 2 groups (< 75 and 75 years). A substantial increase in the mortality rate was observed both in males and females with systolic blood pressure < 120 mmHg. As we do not yet know precisely which role hypertension plays in the elderly, and the results here obtained showed an associa- tion between high diastolic blood pressure and the E3E3 ge- notype, we cannot consider that the relation represents an additional risk in the individuals with the referred genotype. Future studies on mortality follow-up in the elderly with dif- ferent genotypes may clarify whether this relation is bene- ficial, neutral, or bad.

Of the several biological variables studied, body mass index and diastolic blood pressure showed significant diffe- rences among the most frequent ApoE genotypes. In this case, individuals with the E3E3 genotype had a mean body mass index classified as overweight and a greater diastolic blood pressure. No consistent data allowing a comparison or inference about such findings were found in previously published studies. As this characteristic is usually asso- ciated with an increase in the risk of chronic and degene- rative diseases, would this characteristic have a negative effect in the E3E3 genotype? This question requires better investigation, as does the possibility of a causal or potential relation between body mass index and the ApoE genoty- pes. We should not overlook the possibility that this fin- ding may have occurred by chance, or may have been deter- mined by the small size of the sample.

Analysis of the lifestyle components, such as physical activity, alcohol consumption, and tobacco use, was similar in both groups of genotyped individuals, therefore, elimina- ting the effect of these variables in the results found. Howe- ver, additional studies relating the nutritional profile and behavior could eliminate the possibility that this variable would positively influence the maintenance of E3E4 indivi- duals in the population by these individuals adopting a healthy diet.

As the metabolic relation of ApoE polymorphism is di- rectly related to the lipid profile and some types of dyslipide- mia that lead to the development of atherosclerosis, a de- eper analysis of the association between the lipid profile and ApoE genotypes was performed. ApoE was first repor- ted by Shore and Shore 7 as a VLDL component, and, there- fore, the interest of the initial studies was centered on the at- tempt to understand the role played by this apolipoprotein in the prevalence of cholesterol-induced hyperlipidemia 6,7. The subsequent recognition that ApoE is a protein that binds to the LDL receptor (binding-protein) and that this binding affinity depends on genetically determined isofor- ms accelerated the interest of the specialists in elucidating both ApoE form and function. These studies ended up hel- ping in the understanding of the endogenous and exoge- nous cholesterol pathways and leading to the association of the ApoE genotypes and alleles with chronic and dege-

different populations Populations Frequencies Italians Italians 32 Italians 33 British 31 Veranópolis Central Northern Cambridge RS Italy Italy Genotypic E2/2 0.02 0.013 0.016 0.008 E3/2 0.06 0.009 0.07 0.18 E3/3 0.7 0.79 0.74 0.63 E4/3 0.22 0.095 0.17 0.19 E4/4 0 0 0 0 E4/2 0 0.009 0.004 0 Allelic (gene) e2 0.05 0.06 0.04 0.09 e3 0.84 0.88 0.86 0.79 e4 0.11 0.05 0.1 0.12

nerative diseases, such as cardiovascular diseases and de- mentia 4,6. Throughout these years of investigation of the metabolic role played by ApoE, a large number of articles has been published, but the subject is far from being fully clarified 4.

Table VIII - Comparison of the lipoprotein parameters and ApoE genotypes

Veranópolis Italians 32 Total cholesterol E3E3 204.99±39.28 217±43.4 (mg/dl) E3E4 224.91±55.32 229±48.2 E2E3 185.15±77.14 E2E2 147.7 212±43.1 LDL-c E3E3 133.02±32.8 142.1±37.3 (mg/dl) E3E4 155.56±47.26 151.4±45.5 E2E3 109.2±77.22 E2E2 80.37 138.3±39.7 HDL-c E3E3 46.7±12.72 48.5±9.3 (mg/dl) E3E4 44.8±10.43 49.3±12.7 E2E3 49.96±5.04 E2E2 47.36 46.3±7.5 Total cholesterol E3E3 204.99±39.28 217±43.4 (mg/dl) E3E4 122.64±49.57 120.1±48.7 E2E3 129.83±76.4 E2E2 100 123.5±49.8 Lp(a) E3E3 30.26±27.86 25.9±26.1 (mg/dl) E3E4 29.15±28.32 30±35.4 E2E3 26.73±20.8 E2E2 8.8 20±15