Pleiotropic effect of common variants at ABO glycosyltranferase locus in 9q32 on plasma levels of pancreatic lipase and angiotensin converting enzyme

Takamasa Kayama, Hidetoshi Yamashita, Akira Fukao, Isao Kubota, Takeo Kato, Chifumi Kitanaka, Shinya Sato, Yoshiyuki Ueno, Tsuneo Konta, Yoko Shibata, Tetsu Watanabe, Shuichi Abe, Takuya Miyamoto, Sumito Inoue, Takehiko Miyashita, Kazunobu Ichikawa, Tetsuro Shishido, Takanori Arimoto, Hiroki Takahashi, Satoshi NishiyamaAmi Ikeda, Makoto Daimon, Toru Kawanami, Manabu Wada, Shigeki Arawaka, Hidetoshi Oizumi, Katsuro Kurokawa, Shingi Susa, Yuichi Katou, Wataru Kameda, Shingo Koyama, Shigeru Karasawa, Chifumi Iseki, Yoshimi Takahashi, Sumio Kawata, Takafumi Saito, Naohiko Makino, Kazuo Okumoto, Hiroaki Haga, Takeshi Sato, Chikako Sato, Hisayoshi Watanabe, Yuko Nishise, Rika Ishii, Akiko Matsuda, Tomohiro Tozawa, Kei Honma, Hiroto Narimatsu, Kyoko Shibata, Akiko Miura, Rina Inoue, Ai Numazawa, Kahori Kudo, Yoko Aita, Noriko Umezawa, Yuko Saito, Yumi Takahashi, Yuka Suzuki, Katsumi Otani, Atsushi Hozawa, Li Shao, Masatsugu Orui, Atsuko Kobayashi, Yuka Kanoya, Takiko Hosoya, Ikuko Suzuki, Mariko Otake, Yuko Morikagi, Akiko Sekimata, Manami Hiraka, Yumi Matsuda, Yoko Takeda, Yoko Matsunami, Tatsuya Horie, Shiho Sato, Mizue Inoue, Kaoru Baba, Gen Tamiya, Masao Ueki, Tomohiro Nakamura, Jamiyansuren Jambaldorj, Satoko Araki, Osamu Nakajima, Kazuei Takahashi, Kazuo Goto, Kimishige Ishizaka

Research output: Contribution to journalArticlepeer-review

Abstract

For forty-three clinical test values presumably associated to common complex human diseases, we carried out a genomewide 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.

Original languageEnglish (US)
Article numbere55903
JournalPloS one
Volume9
Issue number2
DOIs
StatePublished - Feb 28 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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