title: Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene with tropical calcific pancreatitis.
abstract: BACKGROUND
  The genetic basis of tropical calcific pancreatitis (TCP) is different and is explained by mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. However, mutated SPINK1 does not account for the disease in all the patients, neither does it explain the phenotypic heterogeneity between TCP and fibro-calculous pancreatic diabetes (FCPD). Recent studies suggest a crucial role for pancreatic renin-angiotensin system during chronic hypoxia in acute pancreatitis and for angiotensin converting enzyme (ACE) inhibitors in reducing pancreatic fibrosis in experimental models. We investigated the association of ACE gene insertion/deletion (I/D) polymorphism in TCP patients using a case-control approach. Since SPINK1 mutations are proposed a modifier role, we also investigated its interaction with the ACE gene variant.
  
  
  METHODS
  We analyzed the I/D polymorphism in the ACE gene (g.11417_11704del287) in 171 subjects comprising 91 TCP and 80 FCPD patients and compared the allelic and genotypic frequency in them with 99 healthy ethnically matched control subjects.
  
  
  RESULTS
  We found 46% and 21% of TCP patients, 56% and 19.6% of FCPD patients and 54.5% and 19.2% of the healthy controls carrying the I/D and D/D genotypes respectively (P>0.05). No significant difference in the clinical picture was observed between patients with and without the del allele at the ACE in/del polymorphism in both categories. No association was observed with the presence or absence of N34S SPINK1 mutation in these patients.
  
  
  CONCLUSIONS
  We conclude that the ACE insertion/deletion variant does not show any significant association with the pathogenesis, fibrosis and progression of tropical calcific pancreatitis and the fibro-calculous pancreatic diabetes.
authors.affiliation: Genome Research Group, Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. seema@ccmb.res.in <seema@ccmb.res.in>
authors.forename: Seema
authors.initials: S
authors.lastname: Bhaskar
authors.forename: D N
authors.initials: DN
authors.lastname: Reddy
authors.forename: Swapna
authors.initials: S
authors.lastname: Mahurkar
authors.forename: G V
authors.initials: GV
authors.lastname: Rao
authors.forename: Lalji
authors.initials: L
authors.lastname: Singh
authors.forename: Giriraj R
authors.initials: GR
authors.lastname: Chandak
mesh_terms: D000328:Adult; D002114:Calcinosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D003920:Diabetes Mellitus / Q000209:etiology / Q000235:genetics; D018450:Disease Progression; D004587:Electrophoresis, Agar Gel; D005260:Female; D005355:Fibrosis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016254:Mutagenesis, Insertional; D050500:Pancreatitis, Chronic / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D007703:Peptidyl-Dipeptidase A