Document Detail


Presence of SPINK-1 variant alters the course of chronic pancreatitis.
MedLine Citation:
PMID:  21375584     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background and Aims: There is growing evidence that genetic mutations/variants increase susceptibility to development and progression of chronic pancreatitis (CP). Several mutations have been identified that have a direct and indirect role in events leading onto to CP. Mutations in the serine protease inhibitor, Kazal type1 (SPINK-1) gene have been reported to lower the threshold for pancreatitis in presence of other genetic or environmental factors. The prevalence and impact of SPINK-1 mutations on the clinical course and outcomes of CP remains unclear. This study was conducted to assess the prevalence of SPINK-1 / N34S variant in patients with CP, and understand the impact of SPINK-1 mutation on the natural history of CP. Methods: A retrospective-prospective analysis of 239 subjects with CP was performed. A detailed history including duration of symptoms, type of pain (intermittent flares or chronic continuous pain), number of flares requiring hospital admission, alcohol and smoking history, and family history was obtained. The baseline morphologic stage of CP was categorized by Cambridge classification. Clinical outcome variables included frequency and severity of pain episodes, presence of exocrine failure (defined by presence of steatorrhea and/or fecal elastase <200ug/gm) and diabetes. The genetic tests included cationic trypsinogen gene mutation (PRSS-1), cystic fibrosis gene mutations (Genzyme assay), and SPINK-1/N34S mutation. Results: Out of 239 subjects with CP, 13 subjects (5.4%) were positive for SPINK-1/N34S mutation. There were 35 (14.6%) subjects with idiopathic pancreatitis (IP) in this cohort. Most of the subjects positive for SPINK-1/N34S mutation were group of subjects with IP and were Caucasian (69.2%). The subjects with SPINK-1/N34S mutation had a younger age of onset {(32.9 ± 10.2 vs 40.1 ± 13.6 yrs) (p = 0.108)} than the subjects with IP and no mutation. Over a median follow up of 9.6 years, the subjects with SPINK-1/N34S mutation had a significantly greater number of acute flares each year as compared to those without the mutation (11.8 ± 1.5 vs 4 ± 0.98) (p = 0.0001). Conclusions: The prevalence of SPINK-1/N34S mutation in patients with CP is 5.4% and is about 37.1% in patients with IP. These mutations are more prevalent in Caucasian patients with CP. The SPINK-1/N34S mutation predisposes to early onset IP and more frequent acute flares of pancreatitis that may ultimately lead on to pancreatic insufficiency. The subjects with IP and borderline alcohol history should be considered for testing for genetic analysis including SPINK-1 mutations, initially restricted to clinical trials.
Authors:
Bimaljit Sandhu; Patrik Vitazka; Andrea Ferreira-Gonzalez; Arti Pandya; Ravi Vachhani; Doumit Bouhaidar; Alvin Zfass; Arun Sanyal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-7
Journal Detail:
Title:  Journal of gastroenterology and hepatology     Volume:  -     ISSN:  1440-1746     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607909     Medline TA:  J Gastroenterol Hepatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Affiliation:
VCU Medical Center - Gastroenterology 1200 E Broad St PO Box 980341, Richmond, Virginia 23298 United States VCU Medical Center - Molecular Diagnostics Richmond, Virginia United States VCU Medical Center - Molecular Diagnostics Richmond, Virginia United States VCU Medical Center - Molecular Diagnostics Richmond, Virginia United States VCU Medical Center - Gastroenterology Richmond, Virginia United States VCU Medical Center - Gastroenterology Richmond, Virginia United States VCU Medical Center - Gastroenterology Richmond, Virginia United States VCU Medical Center - Gastroenterology Richmond, Virginia United States.
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