title: Idiopathic chronic pancreatitis in India: phenotypic characterisation and strong genetic susceptibility due to SPINK1 and CFTR gene mutations.
abstract: OBJECTIVE
  To study the genetic predisposition, phenotype and prognosis of idiopathic chronic pancreatitis (CP).
  
  
  METHODS
  Prospective observational and case-control study.
  
  
  METHODS
  Tertiary care academic centre.
  
  
  METHODS
  Consecutive patients with CP.
  
  
  METHODS
  Detailed mutational analysis was done for the cationic trypsinogen, SPINK1 and CFTR genes with single-strand conformational polymorphism or restricted fragment length polymorphism, and sequencing. Clinical and disease characteristics of idiopathic versus alcoholic CP, and early onset versus late onset idiopathic CP were compared. Response to multimodality treatment (medical, endoscopic and/or surgical) and prognosis were analysed.
  
  
  METHODS
  Genetic mutations, phenotypic characterisation and prognosis of idiopathic CP.
  
  
  RESULTS
  Of the 411 patients with CP, 242 had idiopathic aetiology (age 27.50+/-11.85 years; 154 men). Malnutrition and cassava were not risk factors. SPINK1 N34S mutation was present in 42% of patients with idiopathic CP (vs 4% controls, p<0.001) and 17% of patients with alcoholic CP (p=0.016 compared with controls). In the CFTR gene, nine patients with idiopathic CP had mutations and 41 patients had polymorphisms (50% vs 10% controls, p<0.001). Diabetes developed in 35.53% of patients with idiopathic CP. About 85% of patients had significant pain relief with therapy. The probability of surviving for 35 years after onset of idiopathic CP was 83%. The typical features of tropical calcific pancreatitis were seen only in 5.8% of patients.
  
  
  CONCLUSIONS
  Strong genetic susceptibility due to SPINK1 and CFTR gene mutations, and comparative phenotype of idiopathic CP in India suggest that the term 'tropical calcific pancreatitis' is a misnomer.
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India.
authors.forename: Shallu
authors.initials: S
authors.lastname: Midha
authors.forename: Rajni
authors.initials: R
authors.lastname: Khajuria
authors.forename: Shivaram
authors.initials: S
authors.lastname: Shastri
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kabra
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Garg
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D009752:Nutritional Status; D019512:Pancreatitis, Alcoholic / Q000235:genetics; D050500:Pancreatitis, Chronic / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014359:Trypsin Inhibitor, Kazal Pancreatic; D055815:Young Adult
chemical_list: C505032:CFTR protein, human; D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic