engleski

APOE E4 allele - the negative predictor of longevity

The apolipoprotein E (APOE) gene is one of the rare candidate genes consistently found to be associated with the longevity. Its product, ApoE enzyme, is essential for the normal catabolism of total and LDL-cholesterol, and therefore highly correlates with the risk for the development of atherosclerotic cardiovascular disease (CVD) and dementia. We tested the association of APOE gene epsilon polymorphisms (combinations of rs429358 and rs7412) with longevity, CVD risk factors and CVD endpoints in the Croatian 80+ population (80-101 yrs ; mean=88.28 yrs ; N=324 ; 74.4% of women ; 65.1% hypertensives). None of our E44 genotype carriers was older than 95 years (p=0.034), which suggested E4 being a risk allele that does not contribute to longevity. This result was confirmed by the meta-analysis of E4 allele frequencies in general population compared with 80+ yrs population: E4 allele was more frequent in younger people in all 14 tested European populations (p<0.001). In addition to meta-analysis, we found correlations between genetic and geographic distances across Europe (p<0.001). Considering the other tested CVD risk factors, all E4 carriers had waist/ hip ratio ≥0.80 (p=0.034). At the same time E2 carriers less frequently had elevated LDL-cholesterol levels (p=0.047) and diastolic blood pressure (p=0.033), in comparison with non-carriers. Our findings confirm previously reported deleterious effect of E4 allele to the longevity.

apolipoprotein E (APOE) ; E4 allele ; longevity ; 80+ population ; meta-analysis

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