[Tokyo Centenarian Study. 4. Apolipoprotein E phenotype in Japanese centenarians living in the Tokyo Metropolitan area].

To examine the relationship between apolipoprotein E (apoE) phenotype and life span, we measured the frequently of the apoE phenotype and allele in 54 Japanese centenarians who lived in the Tokyo metropolitan area in 1994, 1995, and 1996. The control group consisted of 973 subjects, 883 healthy volunteers who were described previously and 90 healthy people who came to the Keio health consulting center. The apoE phenotypes in the centenarians was 2 E2/E2 (3.7%), 5 E2/E3 (9.3%), 38 E3/E3 (70.4%), and 9 3E/E4 (16.7%). No other phenotype was observed. In the control group, the phenotypes were 2 E2/E2 (0.2%), 57 E2/E3 (5.9%) 712 E3/E3 (73.2%), and 179 E3/E4 (18.4%). The frequency of E2 was higher in the centenarians. The frequencies of the apoE allele in the centenarians and the control subjects were epsilon 2 8.3% vs. 3.5%, epsilon 3 83.3% vs. 85.4%, and epsilon 4 8.3% vs. 10.9%. The frequency of the apoE allele differed significantly between centenarians and control subjects (chi 2 = 6.84, p = 0.033). Levels of serum cholesterol and apolipoprotein B were significantly lower in the E2/E2 + E2/E3 centenarians. Studies of the frequency of the apoE allele in Japanese, French, and Finnish subjects showed that epsilon 2 is more frequent and epsilon 4 is less frequent in centenarians. These data show the apoE phenotype may affect life span: epsilon 2 is positively and epsilon 4 is negatively associated with longevity.

[1]  Jonathan D. Smith,et al.  Apolipoprotein E allele–specific antioxidant activity and effects on cytotoxicity by oxidative insults and β–amyloid peptides , 1996, Nature Genetics.

[2]  T. Asada,et al.  Prevalence of Dementia and Distribution of ApoE Alleles in Japanese Centenarians: An Almost‐Complete Survey in Yamanashi Prefecture, Japan , 1996, Journal of the American Geriatrics Society.

[3]  G. Siest,et al.  Apolipoprotein E: an important gene and protein to follow in laboratory medicine. , 1995, Clinical chemistry.

[4]  M. Gearing,et al.  Apolipoprotein E genotype in diverse neurodegenerative disorders , 1995, Annals of neurology.

[5]  R. Tilvis,et al.  Aging and genetic variation of plasma apolipoproteins. Relative loss of the apolipoprotein E4 phenotype in centenarians. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[6]  A. M. Saunders,et al.  Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease , 1994, Nature Genetics.

[7]  R. Mahley,et al.  Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. , 1994, Science.

[8]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[9]  K. Watanabe,et al.  A racial difference in apolipoprotein E allele frequencies between the Japanese and Caucasian populations , 1986, Clinical genetics.

[10]  K. Yamakawa,et al.  Frequencies of apolipoproteins E5 and E7 in apparently healthy Japanese , 1985, Japanese Journal of Human Genetics.

[11]  P. Froguel,et al.  Genetic associations with human longevity at the APOE and ACE loci , 1994, Nature Genetics.