IN SEARCH OF A BIOLOGICAL PATTERN FOR HUMAN LONGEVITY - IMPACT OF APOA-IV GENETIC POLYMORPHISMS ON LIPOPROTEINS AND THE HYPER-LP(A) IN CENTENARIANS

We studied centenarians to investigate the biological basis of human l ongevity focusing on the apolipoprotein A-IV and lipoprotein(a), poten tially involved in the susceptibility to atherogenic mechanisms. We an alyzed two restriction polymorphisms, HinfI(347) (alleles +, -) and Fn u4HI(360) (alleles 1, 2), and a VNTR (alleles 3, 4) at the 3' region o f the apo A-IV gene. The allele frequencies, the lipoprotein concentra tions and their association in centenarians and adults have been compa red. In centenarians, the HinfI genotype distribution is different (P< 0.05) and the (+13) haplotype is prevalent (0.54 vs. 0.39), with a gre ater association of (+3), indicating the selection of a favourable all ele. The lipoprotein modulation by the apo A-IV polymorphisms is sugge sted by significant associations in adults ((+/+) homozygotes have low er LDL-cholesterol and apo B than heterozygotes; (1/1) homozygotes hav e higher TG and apo B than heterozygotes), that in centenarians still exists as a trend. Centenarians show peculiar lipoprotein features: lo wer LDL-cholesterol (mean 103 vs. 115 mg/dl; P < 0.02), and higher lip oprotein(a) (median 17.5 vs. 4.5; P < 0.002). Large part of them (47%) , especially the Hinf(+/+) and the (+13) homozygotes, have a lipoprote in(a) >20 mg/dl, value considered as the threshold for atherogenic ris k, surprisingly compatible with healthy longevity. (C) 1998 Elsevier S cience Ireland Ltd. All rights reserved.