title: Limited contribution of the SPINK1 N34S mutation to the risk and severity of alcoholic chronic pancreatitis: a report from the United States.
abstract: Mutations in the SPINK1 gene (e.g. N34S) have been reported in patients with idiopathic, familial, tropical, and alcoholic pancreatitis. The prevalence of SPINK1 N34S differs between different patient populations, and its contribution to the risk and the severity of alcoholic chronic pancreatitis has not been defined in the United States. Mutational analysis of the exon 3 was performed in 32 patients with alcoholic chronic pancreatitis, 39 patients with nonalcoholic chronic pancreatitis or recurrent acute pancreatitis, and 190 previously studied healthy controls. The course of alcoholic chronic pancreatitis with and without N34S was compared in age of onset- and sex-matched patients. All SPINK1 gene sequence variations were heterozygous. SPINK1 N34S was present in 3/190 (1.6%) and P55S was found in 2/190 (1.1%) of controls. In alcoholics, the N34S mutation was identified in 2/32 patients (6.3%, P > 0.05). In nonalcoholics, N34S and P55S were identified in 6/39 patients (15.4%, P < 0.005, N34S N = 4, P55S N = 1, N34S/P55S N = 1). The clinical course of alcoholic chronic pancreatitis was similar between patients with and without the N34S mutation. The N34S mutation is uncommon in patients with alcoholic chronic pancreatitis in the United States; its prevalence is similar to other countries and appears not to alter the onset or the severity of alcoholic chronic pancreatitis.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Center for Genomic Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schneider
authors.forename: Roland H
authors.initials: RH
authors.lastname: Pfützer
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.forename: Adam
authors.initials: A
authors.lastname: Slivka
authors.forename: John
authors.initials: J
authors.lastname: Martin
authors.forename: David C
authors.initials: DC
authors.lastname: Whitcomb
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D019512:Pancreatitis, Alcoholic / Q000235:genetics*; D015995:Prevalence; D012720:Severity of Illness Index; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics*; D014481:United States
chemical_list: D014359:Trypsin Inhibitor, Kazal Pancreatic