title: Divergent roles of SPINK1 and PRSS2 variants in tropical calcific pancreatitis.
abstract: OBJECTIVE
  Tropical calcific pancreatitis (TCP) refers to a type of idiopathic pancreatitis prevalent in Asia. The trypsin inhibitor (SPINK1) N34S variant partially explains the genetic susceptibility to TCP. As anionic trypsinogen (PRSS2) G191R protects against chronic pancreatitis in Europeans, we investigated whether this variant protects from TCP in Indians.
  
  
  METHODS
  We enrolled 174 patients and 794 controls from two Indian tertiary care referral hospitals. We analyzed PRSS2 and SPINK1 variants by melting curve analysis, allele-specific discrimination assay, and sequencing.
  
  
  RESULTS
  G191R was detected in 1 TCP patient (0.6%) compared to 13 controls (1.6%; OR 0.27, 95% CI 0.03-2.1; p = 0.33). SPINK1 N34S was enriched in the TCP population 67/174 (38.5%) compared to controls 10/234 (4.3%; OR 14, 95% CI 6.9-28.3; p < 0.001).
  
  
  CONCLUSIONS
  G191R PRSS2 is a rare allele in the Indian population and the data suggest a nonsignificant trend towards a protective effect. N34S SPINK1 represents the major genetic risk factor in TCP.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
authors.forename: Santhosh
authors.initials: S
authors.lastname: Sundaresan
authors.forename: Ashok
authors.initials: A
authors.lastname: Chacko
authors.forename: Amit K
authors.initials: AK
authors.lastname: Dutta
authors.forename: Eesh
authors.initials: E
authors.lastname: Bhatia
authors.forename: Heiko
authors.initials: H
authors.lastname: Witt
authors.forename: René H M
authors.initials: RH
authors.lastname: Te Morsche
authors.forename: Jan B M J
authors.initials: JB
authors.lastname: Jansen
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002114:Calcinosis / Q000453:epidemiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D050500:Pancreatitis, Chronic / Q000453:epidemiology / Q000235:genetics*; D014357:Trypsin / Q000235:genetics* / Q000502:physiology*; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen / Q000235:genetics* / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C486642:SPINK1 protein, human; C064831:PRSS2 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; D014357:Trypsin