"Loss of function" mutations in the cationic trypsinogen gene (PRSS1) may act as a protective factor against pancreatitis.
Several genetic factors have been well known to predispose one to chronic pancreatitis (CP). However, little is known about the genetic factors that may provide a protective effect against the disease. Having found a nonsense mutation (c.111C>A; Y37X) and a splicing mutation (IVS2+1G>A) in the cationic trypsinogen gene (protease, serine, 1; PRSS1) in alcoholics without the development of CP, but not in alcoholics with CP and patients with hereditary or idiopathic CP, we propose that while "gain of function" mutations in the PRSS1 gene predispose one to pancreatitis, "loss of function" mutations in the gene may protect one against the disease.
Chen
Jian-Min
JM
INSERM-EMI 01 15, Génétique Moléculaire et Génétique Epidémiologique, Université de Bretagne Occidentale, Etablissement Français du Sang-Bretagne, Centre Hospitalier Universitaire de Morvan, Brest, France.
Le Maréchal
Cedric
C
Lucas
Danièle
D
Raguénès
Odile
O
Férec
Claude
C
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics; D002908:Chronic Disease; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010195:Pancreatitis / Q000235:genetics*; D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics*
D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin