Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis.

;

:

–

Asada T, Yamagata Z, Kinoshita T, et al. Prevalence of dementia and distribution of Ap

alleles in Japanese centenarians: an almost- complete survey in Yamanashi prefecture, Japan. J Am Geriatr Soc.

;

:

–

Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion/ deletion polymorphism of the human angiotensin conversing enzyme gene (DCP

dipeptidyl carboxypeptidase

). Nucl Acids Res.

;

:

Hugher CP, Berg L, Danziger WL, et al. A new clinical scale for the staging of dementia. Br J Psychiatry

;

:

–

Arai Y, Hirose N, Yamamura K, et al. Serum insulin-like growth factor-

in centenarians: implications of IGF-

as a rapid turnover protein. J Gerontol Med Sci.

;

A:M

–M

Silver MH, Jilinskaia E, Perls TT. Cognitive functional status of age- confirmed centenarians in a population-based study. J Gerontol Psych Sci.

;

B:P

–P

Lindpaintner K, Lee M, Larson MG, et al. Absence of association of genetic linkage between the angiotensin converting-enzyme gene and left ventricular mass. N Engl J Med.

;

:

–

Higashimori K, Zhao Y, Higaki J, et al. Association analysis of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population. Biochem Biophys Res Commun.

;

:

–

Hu J, Miyatake F, Aizu Y, et al. Angiotensin-converting enzyme genotype is associated with Alzheimer disease in the Japanese popu- lation. Neurosci Lett.

;

:

–

Rebeck GW, Perls TT, West HL, et al. Reduced apolipoprotein epsilon

allele frequency in the oldest old. Alzheimer’s patients and cog- nitively normal individuals. Neurology.

;

:

–

Perls T. Genetic and Phenotypic markers among centenarians. J Ger- ontol Med Sci.

;

A:M

–M

Gerdes LU, Jeune B, Ranberg KA, et al. Estimation of apolipoprotein E genotype-specific relative mortality risks from the distribution of genotypes in centenarians and middle-aged men: Apolipoprotein E gene is a ‘‘ frailty gene,’’ not a ‘‘ longevity gene.’’ Genet Epidemiol.

;

:

–

Ariel PM, Richard M, Colleen N, Steven S, Lars B. Association of Apo E polymorphism with plasma lipid levels in a multiethnic elderly population. Arterioscler Thromb Vasc Biol.

;

:

–

Song YM, Sung JH. Body mass index and mortality: a twelve-year prospective study in Korea. Epidemiology.

;

:

–

Ki CS, Na DL, Kim HJ, Kim JW. Alpha-

antichymotrypsin and alpha-

macroglobulin gene polymorphisms are not associated with Korean late-onset Alzheimer’s disease. Neurosci Lett.

;

:

–

In summary, the present Korean centenarian study pro- duced rather different results about the effect of ACE and APOE polymorphisms on human longevity and dementia. It is not surprising that Asian people with different genetic and environmental backgrounds show different results from Westerners in research on multifactorial phenomena. Our data disproved the association of the D allele of the ACE gene with longevity and dementia. One possible explanation may be that the effect of the allele is sufficiently mild as to be buffered by environmental and other genetic factors. Nevertheless the limitation of the study due to small sample size needs to be overcome in future research for a definitive conclusion to be made. The genetic polymorphism of APOE was not significantly different between the centenarians and control population. However, e4 allele frequency showed a tendency to decrease at extremely old age. It was found that the unfavorable effect of the e4 allele on dementia status is still remarkable among centenarians.

from http://biomedgerontology.oxfordjournals.org/ at Kungl Tekniska Hogskolan Biblioteket on July 15, 2015

ACKNOWLEDGMENTS

This research was supported by grants from the Ministry of Health and Welfare, the Aging and Apoptosis Research Center (RII-2002-001-01-001), the Korea Research Foundation for Health Science, and Seoul National University Interdisciplinary Research Program.

AddresscorrespondencetoSangChulPark,MD,PhD,DepartmentofBio- chemistry,SeoulNationalUniversityCollegeofMedicine,28Yongon-dong, Chongno-ku, Seoul 110-744, South Korea. E-mail: scpark@snu.ac.kr

at Kungl Tekniska Hogskolan Biblioteket on July 15,

REFERENCES

heritable in a sample of Danish twins born

–

J Gerontol Biol Sci.

;

A:B

–B

Ljungquist B, Berg S, Lanke J, et al. The effect of genetic factors for longevity: A comparison of identical and fraternal twins in the Swedish Twin Registry. J Gerontol Med Sci.

;

A:M

–M

Perls T, Wager C, Bubrick E, et al. Siblings of centenarians live longer. Lancet.

;

:

Perls T, Kunkel LM, Puca AA. The Genetics of Exceptional Human Longevity. J Am Geriatr Soc.

;

:

–

Takata H, Suzuki M, Ishii T, et al. Influence of major histocompatibility complex region genes on human longevity among Okinawan-Japanese centenarians and nonagenarians. Lancet.

;

:

–

Sha¨chter F, Fauer-Delanf L, Guenot F, et al. Genetic association with human longevity at the apo E and ACE loci. Nature Genet.

;

:

–

Rahmutula D, Nakayama T, Izumi Y, et al. Angiotensin-converting en- zyme gene and longevity in the Xin Jiang Uighur autonomous region of China: an association study. J Gerontol Med Sci.

;

A:M

–M

Frisoni GB, Louhija J, Geroldi C, Trabucchi M. Longevity and the e

allele of apolipoprotein E: the Finnish centenarians study. J Gerontol Med Sci.

;

A:M

–M

De Benedictis G, Falcone E, Rose G, et al. DNA Multiallelic systems reveal gene/longevity associations not detected by diallelic systems. The APOB locus. Hum Genet.

;

:

–

Blanche H, Cabanne L, Sahbatou M, Thomas G. A study of French centenarians: are ACE and APOE associated with longevity? Comptes Rendus de l’Academie des Sciences–Serie III, Sciences de la Vie.

;

:

–

Cambien F, Poirier O, Lecerf L, et al. Deletion polymorphism in the myocardial infarction. Nature.

;

:

–