Genetic variants in PCSK9 affect the cholesterol level in Japanese (original) (raw)

• Short Communication
• Published: 01 February 2004
• Toshifumi Mannami3,
• Yoshihiro Kokubo3,
• Nozomu Inamoto3,
• Shuichi Takagi4,
• Yoichi Goto4,
• Hiroshi Nonogi4 &
• …
• Naoharu Iwai1

Journal of Human Genetics volume 49, pages 109–114 (2004)Cite this article

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Abstract

Mutations in the proprotein convertase subtilisin/kexin 9 (PCSK9) gene have been reported in affected members of two families with autosomal dominant hypercholesterolemia. To investigate the effects of common variants in PCSK9 on the cholesterol level, we conducted an association study using a large cohort representing the general population in Japan (_n_=1,793). Direct sequencing in all of the exonic regions identified 21 polymorphisms. After consideration of linkage disequilibrium among these polymorphisms, we selected and genotyped nine polymorphisms by the TaqMan method. The intron 1/C(-161)T and exon 9/I474 V polymorphisms were associated with levels of total cholesterol (TC) [C(-161)T, _P_=0.0285; I474 V, _P_=0.0069] and low-density lipoprotein cholesterol (LDL-C) [C(-161)T, _P_=0.0257; I474 V, _P_=0.0007]. The distributions of these polymorphisms in subjects with miocardial infarction (MI) (_n_=649) were not different from those in the control population. These results provide the first evidence that common variants intron 1/C(-161)T and exon 9/I474 V in PCSK9 significantly affect TC and LDL-C levels in the general population in Japan.

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Acknowledgements

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 very grateful to Dr. Soichiro Kitamura, President of the National Cardiovascular Center, for his support of our research. We would 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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Authors and Affiliations

1. Department of Epidemiology, Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai Suita, Osaka 565-8565, Japan
   Keisuke Shioji & Naoharu Iwai
2. The Organization for Pharmaceutical Safety and Research of Japan, Tokyo, Japan
   Keisuke Shioji
3. Department of Preventive Cardiology, National Cardiovascular Center, Osaka, Japan
   Toshifumi Mannami, Yoshihiro Kokubo & Nozomu Inamoto
4. Division of Cardiology, National Cardiovascular Center, Osaka, Japan
   Shuichi Takagi, Yoichi Goto & Hiroshi Nonogi

Authors

1. Keisuke Shioji
2. Toshifumi Mannami
3. Yoshihiro Kokubo
4. Nozomu Inamoto
5. Shuichi Takagi
6. Yoichi Goto
7. Hiroshi Nonogi
8. Naoharu Iwai

Corresponding author

Correspondence toNaoharu Iwai.

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Shioji, K., Mannami, T., Kokubo, Y. et al. Genetic variants in PCSK9 affect the cholesterol level in Japanese.J Hum Genet 49, 109–114 (2004). https://doi.org/10.1007/s10038-003-0114-3

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• Received: 29 September 2003
• Accepted: 17 November 2003
• Published: 01 February 2004
• Issue Date: February 2004
• DOI: https://doi.org/10.1007/s10038-003-0114-3

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