Genetic Polymorphism and Nutrition of Japanese Yasuo Kagawa, Yoshiko Yanagisawa, Mieko Abe and Aya Sato Department of Medical Chemistry, Kagawa Nutrit

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1 Genetic Polymorphism and Nutrition of Japanese Yasuo Kagawa, Yoshiko Yanagisawa, Mieko Abe and Aya Sato Department of Medical Chemistry, Kagawa Nutrition University Lifestyle related diseases including hypertension, diabetes, obesity and hypercholesterolemia are the results of both genetic and environmental factors. The genetic factor is mainly composed of single nucleotide polymorphism (SNP) and environmental factors include diet, exercise, drinking and smoking. The ethnic difference in the frequency of SNP may be caused by natural selection depending on the types of agricultures in human history. The resistance against starvation among Japanese is caused by many SNPs including those in beta adrenergic receptor, uncoupling proteins, calpain 10, PPAR-gamma, leptin receptor. Hypertension of Japanese is also caused by SNP for factors retaining salt, such as angiotensinogen, aldosterone synthase and angiotensin converting enzyme. T type SNP of angiotensinogen was needed for apes living in the tropical forest, but is predisposing hypertension in the modern society. The ethnic differences in digestion of lactase may be the result of Rabi agriculture, those in aldehyde dehydrogenase and gulonolactone dehydrogenase are caused by the tropical foods. Japanese diet is based on the Ubi agriculture of Jomon era since 10, 000 years before present (YBP), and rice growing of Yayoi era since 3,000 YBP. However, there are strong impacts of westernization including that of Rabi agriculture after We have studied SNPs in Palau as a model of Mongoloids because of their rapid increase in diabetes by westernization. SNPs saving energy were found in PPAR gamma, UCP3 promotor, leptin receptor etc. (Biochem. Biophys. Res. Commun., 281, 772, 2001). We also analyzed SNPs of the patients who were educated years ago. Despite differeces in SNPs (betaadrenergic receptor, apoe and mtdna), the special dietary habits (four group point method) prevented most of the lifestyle related diseases. Finally, total analysis of mtdna from patients of encephalomyopathy detected three new mutation points. In conclusion, the merit of traditional Japanese diet will prevent Japanese from obesity and diabetes mellitus, because of their special SNPs regulating metabolism. Jpn. J. Nutr., 59 (5) 213 `220 (2001)

8 10) Yanagisawa, Y., Hasegawa, K., Dever, G.J., Otto, C.T.O., Sakuma, M., Shibata, S., Miyagi, S., Kaneko, Y. and Kagawa, Y.: Uncoupling protein 3 and Biophys. Res. Commun., 281, (2001) 11) Kagawa, Y. and Kagawa, A.: Secondary pre- vention of cardiovascular diseases of outpatients of the Nutrition Clinic, In Nutritional Prevention of Apolipoprotein E genetic variation and Alzheimer's disease. a meta-analysis, Dement. Geriatr. Cogn. Disorder, 10, (1999) 3) Kagawa, Y.: Impact of westernization on nutrition of Japanese, Prevent. Med., 7, (1978) 4) Fujisawa, T., Ikegami, H., Kawaguchi, Y. and Ogihara, T.: Meta-analysis of the association of Trp64Arg polymorphism of beta 3-adrenergic receptor gene with body mass index, J. Clin. Endocrinol. Metab., 83, (1998) 5) CODE Genetics Incorporated, Gulcher, J.R., Kong, A. and Stefansson, K.: The role of linkage studies for common diseases, Curr. Opinion Genet. Dev., 11, (2001) 6) Staessen, J.A., Kuznetsova, T., Wang, J.G., Emelianov, D., Vlietinck, R. and Fagard, R.: M235T angeiotensinogen gene polymorphism and cardiovascular renal risk, I Hypertens., 17, 9-17 (1999) 7) Hunt, S.C., Cook, N.R., Oberman, A., Cutler, J.A., Hennekens, C.H., Allender, P.S., Walker, W.G., Whelton, P.K. and Williams, R.R.: Angiotensinogen genotype, sodium reduction, weight loss, and prevension of hypertension. Trials of hypertension II, Hypertension, 32, (1998) prevention Phase 8) Colin, P.R.: The dietary approaches to stop hypertension (DASH) clinical trial: implications for lifestyle modifications in the treatment patients, Cardiol. Rev., 7, (1999) of hypertensive 9) Hara, H., Egusa, G. and Yamakido, M.: Incidence of non-insulin-dependent and its risk factors in Japanese-Americans diabetes mellitus living in Hawaii and Los Angeles, Diabet. Med., 13, S (1996) peroxisome proliferator-activated receptor y 2 contribute to obesity and diabetes in Palauans, Biochem. Cardiovascular Diseases/Lovenberg, W. and Yamori, Y. eds. (1984) Academic Press, New York 12) Rubinsztein, D.C. and Easton, D.F.: 13) McCarron, M.O., Delong, D. and Alberts, M.J.: ApoE genotype as a risk factor for ischemic cardiovascular disease: a meta-analysis, Neurology, 53, (1999) 14) Andrews, R.M., Kubacka, I., Cinnery, P.F., Lightowlers, R.N., Turnbull, D.M. and Howell, N.: Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA, Nature Genet., 23, 147 (1999) 15) Matsunaga, H., Tanaka, Y., Tanaka, M., Gong, J.S., Zhang, J., Nomiyama, T., Ogawa, O., Ogihara, T., Yamada, Y., Yagi, K. and Kawamori, R.: Anti-atherogenic mitochondrial genotype in patients with type 2 diabetes, Diabetes Care, 24, (2001) 16) Wilmut, L, Schnieke, A.E., McWhir, J., Kind, A. J. and Campbell, K. H.: Viable offspring derived from fetal and adult mammalian cells, Nature, 385, (1997) 17) Brenner, C.A., Barritt, J.A., Willadsen, S. and Cohen, J.: Mitochondrial DNA heteroplasmy after human ooplasmic transplantation, Fertil. Steril., 74, (2000) 18) Kagawa, Y., Inoki, Y. and Endo, H.: Gene therapy by mitochondrial transfer, Adv. Drug. Deliv. Rev., 49, 107 (2001) 19) Hiraoka, M.: Nutritional status of vitamin A, E, C, Bi, B2, B6, nicotinic acid, B12, folate, and betacarotene in young women, J. Nutr. Sci. Vitaminol., 47, (2001)

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