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

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 ide...

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Published in:Gut Vol. 64; no. 4; pp. 646 - 656
Main Authors: Weiss, Frank Ulrich, Schurmann, Claudia, Guenther, Annett, Ernst, Florian, Teumer, Alexander, Mayerle, Julia, Simon, Peter, Völzke, Henry, Radke, Dörte, Greinacher, Andreas, Kuehn, Jens-Peter, Zenker, Martin, Völker, Uwe, Homuth, Georg, Lerch, Markus M
Format: Journal Article
Language:English
Published: England BMJ Publishing Group LTD 01.04.2015
Subjects:
ABO Blood-Group System - physiology
Adult
Aged
Aged, 80 and over
Antigens
Blood groups
Consent
Enzymes
Female
Fucosyltransferases - physiology
Galactoside 2-alpha-L-fucosyltransferase
Genetic Association Studies
Genome-Wide Association Study
Genomes
Humans
Lipase - blood
Male
Middle Aged
Oils & fats
Pancreatic cancer
Pancreatitis, Chronic - epidemiology
Pancreatitis, Chronic - genetics
Polymorphism, Single Nucleotide
Population
Risk Assessment
Rodents
Studies
Young Adult
Pancreatic Enzymes
Chronic Pancreatitis
Linkage Analysis
Glycosyltransferases
Genetic Polymorphisms
ISSN:0017-5749, 1468-3288, 1468-3288
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Summary: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.
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ISSN:0017-5749
1468-3288
1468-3288
DOI:10.1136/gutjnl-2014-306930