Abstract
Association studies were performed to confirm the effect of polymorphisms in apolipoprotein A1 (ApoA1) on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI). A sequence analysis identified nine polymorphisms in ApoA1. After considering linkage disequilibrium, four polymorphisms in ApoA1 and four polymorphisms in the 5′-flanking regions and 3′-flanking regions from the JSNP database were determined in 1,880 subjects recruited from the Suita study, which represents the general population in Japan. Of the eight polymorphisms tested, the ApoA1 T84C polymorphism had the greatest effect on the levels of HDL-C (P=0.0005, P c=0.0040 corrected by the Bonferroni method) and triglyceride (P<0.0001, P c=0.0008). The ApoA1 MspI polymorphism was not associated with HDL-C or triglyceride levels. We confirmed that the ApoA1 T84C polymorphism was associated with the HDL-C level but not the triglyceride level in patients with MI (n=637). Moreover, this polymorphism was associated with the incidence of MI in male subjects (P=0.0326). A logistic analysis indicated that the frequency of MI in the CC genotype was lower than that in the CT+TT genotype (P=0.0145, OR=0.4955, 95% CI: 0.2746–0.8525). The ApoA1 T84C polymorphism is an important marker for the HDL-C level and may be a new risk marker for MI in Japanese.
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Acknowledgments
This study was supported by the Program for the Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research of Japan. We are deeply grateful to Dr. Soichiro Kitamura, President of the National Cardiovascular Center, for his support of our research. We would like to thank Dr. Mitsuo Matsuda for stimulating discussions. We would also like to thank Dr. Otosaburo Hishikawa, Dr. Katsuyuki Kawanishi, and Mr. Shigeru Kobayashi for their continuous support of our population survey in Suita City. We also thank the members of the Satsuki-Junyukai.
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This study was supported by the Program for the Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research of Japan.
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Shioji, K., Mannami, T., Kokubo, Y. et al. An association analysis between ApoA1 polymorphisms and the high-density lipoprotein (HDL) cholesterol level and myocardial infarction (MI) in Japanese. J Hum Genet 49, 433–439 (2004). https://doi.org/10.1007/s10038-004-0172-1
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DOI: https://doi.org/10.1007/s10038-004-0172-1
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