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Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3495-3504

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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3495-3504.)
© 1997 American Heart Association, Inc.


Articles

Association of Apolipoprotein Genetic Polymorphisms With Plasma Cholesterol in a Japanese Rural Population

The Shibata Study

Mohammad Mostafa Zaman; Shinji Ikemoto; Nobuo Yoshiike; Chigusa Date; Tetsuji Yokoyama; ; Heizo Tanaka

From the Department of Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan (M.M.Z., T.Y., H.T.); the Division of Clinical Nutrition, National Institute of Health and Nutrition, Tokyo, Japan (S.I.); the Division of Adult Health Science, National Institute of Health and Nutrition, Tokyo, Japan (N.Y.); and the Department of Public Health, Osaka City University School of Medicine, Osaka, Japan (C.D.).

Correspondence to Dr Mohammad Mostafa Zaman, Department of Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo, 101 Japan. E-mail zaman.epi{at}mri.tmd.ac.jp

Abstract The association between apolipoprotein (apo) genetic polymorphisms and lipid phenotypes remains to be determined because such studies have reported contradictory results. We have measured plasma total cholesterol (TC) and HDL cholesterol (HDL-C) in a cross-sectional sample of 1328 (462 men and 866 women) Japanese (aged 40 to 80 years) and analyzed their DNA for the following genotypes: apoA1-C3 Msp I and Sst I sites; apoB signal peptide insertion/deletion, Xba I site and 3' variable number of tandem repeats (VNTR); and apoE. Using multivariate analyses (ANOVA) we found that (1) the polymorphisms of apoA1-C3 and apoB genes are not significantly associated with TC or HDL-C and (2) the polymorphism of the apoE gene is significantly related with TC and the TC:HDL-C ratio. The {epsilon}2 carriers have lower levels of TC and a lower TC:HDL-C ratio, {epsilon}3 carriers have intermediate levels, and {epsilon}4 carriers have higher levels. These findings held whether sexes were analyzed separately or together. Although an opposite trend in HDL-C levels was observed, it did not reach the level of statistical significance. Multiple regression analyses have shown that apoE polymorphism accounts for about 2.3% of the variation in TC and TC:HDL-C ratio irrespective of sex. When the subjects are divided into two groups according to their age (<=59 and >=60 years old), the effect of apoE alleles on serum cholesterols appears to be diluted in the younger age group whereas it appears to be accentuated in the older group for both sexes. Our findings suggest that among the apo genetic polymorphisms examined, the apoE gene may be considered as a possible candidate for the "high-risk" strategy of atherosclerosis prevention in the Japanese population.


Key Words: apolipoprotein genes • plasma cholesterol • Japanese population




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