Tropical calcific pancreatitis and its association with CTRC and SPINK1 (p.N34S) variants

Monique H.M. Derikx, Richard Szmola, Rene H.M. Te Morsche, Santhosh Sunderasan, Ashok Chacko, Joost P.H. Drenth

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20 Citations (Scopus)


BACKGROUND: Tropical calcific pancreatitis (TCP) is a relatively common form of chronic pancreatitis in parts of Asia and Africa. The SPINK1 variant p.N34S is strongly associated with TCP, but other genetic factors remain to be defined. Chymotrypsinogen C (CTRC) degrades trypsinogen and loss-of-function variants have been found in European patients with chronic pancreatitis. Preliminary data indicate that CTRC might increase the risk for TCP. MATERIALS AND METHODS: We selected 150 Indian TCP patients and 150 Indian controls to perform mutational screening of the complete coding region of CTRC and exon 3 of SPINK1. We performed in-silico analysis and functional studies of novel CTRC variants. RESULTS: We identified eight variants among this sample. Three were synonymous and c.180 C>T was significantly enriched in patients (odds ratio=2.09; 95% confidence interval=1.19-3.67; P=0.03). We identified a novel nonsynonymous CTRC (p.G61R) variant in one of 146 patients (0.7%), but absent from controls. In-silico analysis showed that this variant affected a conserved residue, and functional analysis showed that p.G61R results in a complete loss of CTRC secretion from transiently transfected human embryonic kidney 293T cells. SPINK1 p.N34S was present in 31.8% of patients compared with 4.7% in controls, there was no significant cosegregation with CTRC variants. CONCLUSION: The contribution of CTRC variants to TCP is relatively small, but the identification of novel loss-of-function variants (p.G61R) underscores the importance of the trypsinogen pathway in causing TCP.

Original languageEnglish
Pages (from-to)889-894
Number of pages6
JournalEuropean Journal of Gastroenterology and Hepatology
Issue number8
Publication statusPublished - Aug 2009



  • Chymotrypsinogen C
  • SPINK1
  • Tropical calcific pancreatitis
  • Trypsinogen

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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