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

PLoS One. 2014 Feb 28;9(2):e55903. doi: 10.1371/journal.pone.0055903. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study / methods*
  • Glycosyltransferases / blood*
  • Humans
  • Peptidyl-Dipeptidase A / blood*
  • Polymorphism, Single Nucleotide / genetics

Substances

  • Glycosyltransferases
  • Peptidyl-Dipeptidase A

Grants and funding

This project study was fully supported by a Grant-in-aid from the Global Center of Excellence program of the Japan Society for the Promotion of Science, “Formation of an International Network for Education and Research of Molecular Epidemiology” (http://www.jsps.go.jp/english/index.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.