Authors: Pepe G; Di Perna V; Resta F; Lovecchio M; Chimienti G; Colacicco AM; Capurso A
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.Keywords: Adult; Aged; Aged, 80 and over; Aging/*blood/genetics; Apolipoproteins A/*genetics; DNA/analysis; DNA Primers/chemistry; Enzyme-Linked Immunosorbent Assay; Female; Gene Frequency; Genotype; Humans; Lipoprotein(a)/*blood; Lipoproteins/blood; Longevity/*genetics; Male; Middle Aged; Polymerase Chain Reaction; *Polymorphism, Genetic
Date: June 11, 1998
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Pepe G, Di Perna V, Resta F, Lovecchio M, Chimienti G, Colacicco AM, Capurso A (1998) 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. Atherosclerosis 137: 407-17.