AGING AND GENETIC-VARIATION OF PLASMA APOLIPOPROTEINS - RELATIVE LOSSOF THE APOLIPOPROTEIN E4 PHENOTYPE IN CENTENARIANS

We determined the common polymorphism of apolipoprotein E (E2, E3, and E4), apolipoprotein B Xba I polymorphism, and apolipoprotein C-III Ss t I polymorphism in almost all Finnish centenarians alive in 1991 (n=1 79/185). Plasma lipid and lipoprotein levels in different apolipoprote in genotypes were also measured. In comparison with younger Finnish po pulations studied previously, the frequency of the apolipoprotein E ep silon 2 allele was almost twice as high (7.0% versus 4.1%; P<.05) and that of the epsilon 4 allele only approximately one third as high (8.4 % versus 22.7%; P<.001) in the centenarians. Plasma cholesterol and hi gh-density lipoprotein cholesterol levels tended to be lowest in the g roup with the epsilon 2 allele (4.33 mmol/L and 1.41 mmol/L, respectiv ely), intermediate in those with the epsilon 3 allele (4.57 mmol/L and 1.48 mmol/L, respectively), and highest in those with the epsilon 4 a llele (4.82 mmol/L and 1.60 mmol/L, respectively). The frequencies of the apolipoprotein B X1 and X2 alleles (Xba I restriction site absent or present, respectively) among the centenarians and among the young F inns were not significantly different, whereas the apolipoprotein C-II I S2 allele (Sst I restriction site present) occurred more often in th e centenarians (frequency, 12.9%) than in the youngest reference popul ation (frequency, 8.8%; P<.05). Centenarians with the apolipoprotein B X2X2 genotype and apolipoprotein E4 phenotype had a higher mean plasm a cholesterol level than those with the X1X1 genotype and E2 phenotype (5.24 versus 3.43 mmol/L; P<.05). We conclude that genetic variation of apolipoproteins influences blood lipid levels up to very high ages and that the epsilon 4 allele may affect life expectancy adversely.