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Idiopathic chronic pancreatitis in India: phenotypic characterisation and strong genetic susceptibility due to SPINK1 and CFTR gene mutations
  1. Shallu Midha1,
  2. Rajni Khajuria1,
  3. Shivaram Shastri1,
  4. Madhulika Kabra2,
  5. Pramod Kumar Garg1
  1. 1Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
  2. 2Department of Pediatrics (Genetics Division), All India Institute of Medical Sciences, New Delhi, India
  1. Correspondence to Dr Pramod Kumar Garg, Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi 110029, India; pkgarg{at}aiims.ac.in

Abstract

Objective To study the genetic predisposition, phenotype and prognosis of idiopathic chronic pancreatitis (CP).

Design Prospective observational and case–control study.

Setting Tertiary care academic centre.

Patients Consecutive patients with CP.

Interventions 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.

Main outcome measures 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.

Conclusion 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.

  • Chronic pancreatitis
  • tropical pancreatitis
  • SPINK1
  • CFTR
  • genetic mutation
  • genetic polymorphisms
  • ACP
  • alcoholic chronic pancreatitis
  • BMI
  • body mass index
  • CFTR
  • cystic fibrosis transmembrane conductance regulator
  • CP
  • chronic pancreatitis
  • CT
  • CT
  • ERCP
  • endoscopic retrograde cholangiopancreatography
  • ICP
  • idiopathic chronic pancreatitis
  • MRCP
  • magnetic retrograde cholangiopancreatography
  • RFLP
  • restriction fragment length polymorphism
  • SPINK1
  • serine protease inhibitor Kazal type-1
  • SSCP
  • single strand conformational polymorphism
  • TCP
  • tropical calcific pancreatitis

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Footnotes

  • Funding The study was supported by two research grants from the Indian Council of Medical Research. SM received an individual fellowship grant from the Indian Council of Medical Research. The funding agency had no role in study design; or in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Institutional Ethics Committee, New Delhi.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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