title: Fucosyltransferase 2 (FUT2) non-secretor status and blood group B are associated with elevated serum lipase activity in asymptomatic subjects, and an increased risk for chronic pancreatitis: a genetic association study.
abstract: OBJECTIVE
  Serum lipase activities above the threefold upper reference limit indicate acute pancreatitis. We investigated whether high lipase activity-within the reference range and in the absence of pancreatitis-are associated with genetic single nucleotide polymorphisms (SNP), and whether these identified SNPs are also associated with clinical pancreatitis.
  
  
  METHODS
  Genome-wide association studies (GWAS) on phenotypes 'serum lipase activity' and 'high serum lipase activity' were conducted including 3966 German volunteers from the population-based Study-of-Health-in-Pomerania (SHIP). Lead SNPs associated on a genome-wide significance level were replicated in two cohorts, 1444 blood donors and 1042 pancreatitis patients.
  
  
  RESULTS
  Initial discovery GWAS detected SNPs within or near genes encoding the ABO blood group specifying transferases A/B (ABO), Fucosyltransferase-2 (FUT2), and Chymotrypsinogen-B2 (CTRB2), to be significantly associated with lipase activity levels in asymptomatic subjects. Replication analyses in blood donors confirmed the association of FUT-2 non-secretor status (OR=1.49; p=0.012) and ABO blood-type-B (OR=2.48; p=7.29×10(-8)) with high lipase activity levels. In pancreatitis patients, significant associations were found for FUT-2 non-secretor status (OR=1.53; p=8.56×10(-4)) and ABO-B (OR=1.69, p=1.0×10(-4)) with chronic pancreatitis, but not with acute pancreatitis. Conversely, carriers of blood group O were less frequently affected by chronic pancreatitis (OR=0.62; p=1.22×10(-05)) and less likely to have high lipase activity levels (OR=0.59; p=8.14×10(-05)).
  
  
  CONCLUSIONS
  These are the first results indicating that ABO blood type-B as well as FUT2 non-secretor status are common population-wide risk factors for developing chronic pancreatitis. They also imply that, even within the reference range, elevated lipase activities may indicate subclinical pancreatic injury in asymptomatic subjects.
authors.affiliation: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Frank Ulrich
authors.initials: FU
authors.lastname: Weiss
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany The Charles Bronfman Institute for Personalized Medicine, Genetics of Obesity & Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schurmann
authors.affiliation: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Guenther
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Ernst
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Teumer
authors.affiliation: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Mayerle
authors.affiliation: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Simon
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Dörte
authors.initials: D
authors.lastname: Radke
authors.affiliation: Department of Transfusion Medicine, Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
authors.affiliation: Department of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Jens-Peter
authors.initials: JP
authors.lastname: Kuehn
authors.affiliation: Institute of Human Genetics, Otto-von-Guericke-Universität Magdeburg, University Hospital Magdeburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.affiliation: Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lerch
mesh_terms: D000017:ABO Blood-Group System / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005647:Fucosyltransferases / Q000502:physiology*; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006801:Humans; D008049:Lipase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D050500:Pancreatitis, Chronic / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D055815:Young Adult; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D000017:ABO Blood-Group System; D005647:Fucosyltransferases; D008049:Lipase; D000097631:Galactoside 2-alpha-L-fucosyltransferase
keywords: Chronic Pancreatitis; Genetic Polymorphisms; Glycosyltransferases; Linkage Analysis; Pancreatic Enzymes