1. Pleiotropic effect of common variants at ABO Glycosyltranferase locus in 9q32 on plasma levels of pancreatic lipase and angiotensin converting enzyme
- Author
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Hiroto Narimatsu, Akira Fukao, Takuya Miyamoto, Shuichi Abe, Yoko Aita, Kimishige Ishizaka, Takehiko Miyashita, Shingo Koyama, Shingi Susa, Hiroki Takahashi, Takafumi Saito, Yoko Matsunami, Chifumi Kitanaka, Ikuko Suzuki, Shigeki Arawaka, Gen Tamiya, Hisayoshi Watanabe, Wataru Kameda, Li Shao, Yuka Kanoya, Tsuneo Konta, Shiho Sato, Masao Ueki, Naohiko Makino, Jamiyansuren Jambaldorj, Yoshimi Takahashi, Chifumi Iseki, Akiko Miura, Katsuro Kurokawa, Takiko Hosoya, Kazuo Okumoto, Takamasa Kayama, Yoko Takeda, Osamu Nakajima, Kei Honma, Katsumi Otani, Akiko Matsuda, Yumi Matsuda, Shinya Sato, Kazuo Goto, Yuka Suzuki, Atsushi Hozawa, Kyoko Shibata, Sumio Kawata, Yoko Shibata, Masatsugu Orui, Yuko Nishise, Kaoru Baba, Akiko Sekimata, Hidetoshi Oizumi, Tomohiro Tozawa, Tomohiro Nakamura, Yumi Takahashi, Takeshi Sato, Ai Numazawa, Rina Inoue, Shigeru Karasawa, Yuko Saito, Atsuko Kobayashi, Makoto Daimon, Mariko Otake, Takeo Kato, Tetsuro Shishido, Isao Kubota, Takanori Arimoto, Satoshi Nishiyama, Hiroaki Haga, Yuko Morikagi, Ami Ikeda, Yuichi Katou, Yoshiyuki Ueno, Mizue Inoue, Tetsu Watanabe, Hidetoshi Yamashita, Manabu Wada, Rika Ishii, Kazunobu Ichikawa, Tatsuya Horie, Kazuei Takahashi, Noriko Umezawa, Toru Kawanami, Kahori Kudo, Satoko Araki, Sumito Inoue, Manami Hiraka, and Chikako Sato
- Subjects
medicine.medical_specialty ,lcsh:Medicine ,Locus (genetics) ,Gastroenterology and Hepatology ,Peptidyl-Dipeptidase A ,Polymorphism, Single Nucleotide ,Pancreatic Cancer ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,ABO blood group system ,Gastrointestinal Tumors ,Genetics ,Genome-Wide Association Studies ,medicine ,Humans ,Pancreatic lipase ,Genetic Predisposition to Disease ,lcsh:Science ,Biology ,Pancreas ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Population Biology ,biology ,lcsh:R ,Computational Biology ,Cancers and Neoplasms ,Glycosyltransferases ,Angiotensin-converting enzyme ,Plasma levels ,3. Good health ,Endocrinology ,Oncology ,030220 oncology & carcinogenesis ,Genetic Polymorphism ,biology.protein ,Medicine ,lcsh:Q ,Population Genetics ,Research Article ,Genome-Wide Association Study - Abstract
For forty-three clinical test values presumably associated to common complex human diseases, we carried out a genome-wide association study using 600K SNPs in a general Japanese population of 1,639 individuals (1,252 after quality control procedures) drawn from a regional cohort, followed by a replication study for statistically significant SNPs (p = 1.95 × 10(-9)-8.34 × 10(-39)) using an independent population of 1,671 from another cohort. In this single two-stage study, we newly found strong and robust associations of common variants at the ABO histo-blood glycosyltransferase locus in 9q32 with the plasma levels of pancreatic lipase (P-LIP), in addition to successful confirmation of the known ABO association of angiotensin converting enzyme (ACE) independent of the ACE1 gene in 17q23.2 with the ACE level. Our results are compatible with the previously reported association between the ABO gene and pancreatic cancer, and show that the effect of these common variants at the ABO locus on the P-LIP and ACE levels is largely opposing and pleiotropic.
- Published
- 2014