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). 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.