In search of a biological pattern for human longevity: impact of apo A-IV genetic polymorphisms on lipoproteins and the hyper-Lp(a) in centenarians

Abstract

We studied centenarians to investigate the biological basis of human longevity focusing on the apolipoprotein A-IV and lipoprotein(a), potentially involved in the susceptibility to atherogenic mechanisms. We analyzed two restriction polymorphisms, HinfI347 (alleles +, -) and Fnu4HI360 (alleles 1, 2), and a VNTR (alleles 3, 4) at the 3' region of the apo A-IV gene. The allele frequencies, the lipoprotein concentrations and their association in centenarians and adults have been compared. In centenarians, the HinfI genotype distribution is different (P < 0.05) and the (+13) haplotype is prevalent (0.54 vs. 0.39), with a greater association of (+3), indicating the selection of a favourable allele. The lipoprotein modulation by the apo A-IV polymorphisms is suggested by significant associations in adults ((+/+) homozygotes have lower LDL-cholesterol and apo B than heterozygotes; (1/1) homozygotes have higher TG and apo B than heterozygotes), that in centenarians still exists as a trend. Centenarians show peculiar lipoprotein features: lower LDL-cholesterol (mean 103 vs. 115 mg/dl; P < 0.02), and higher lipoprotein(a) (median 17.5 vs. 4.5; P < 0.002). Large part of them (47%), especially the Hinf(+/+) and the (+13) homozygotes, have a lipoprotein(a) > 20 mg/dl, value considered as the threshold for atherogenic risk, surprisingly compatible with healthy longevity.