title: The role of CFTR and SPINK-1 mutations in pancreatic disorders in HIV-positive patients: a case-control study.
abstract: OBJECTIVE
  Pancreatic disorders in HIV-positive patients are frequent. CFTR and SPINK-1 mutations have been reported to increase the risk of pancreatitis, but no data are available in HIV-positive patients. This study will evaluate the frequency of CFTR mutations and SPINK-1 polymorphisms in HIV-positive patients with clinical pancreatitis or asymptomatic elevation of serum pancreatic enzymes.
  
  
  METHODS
  Cases (patients with hyperamylasemia) were identified during a toxicity study conducted in August 1999 among 1152 participants of the Swiss HIV Cohort Study. We designed a case-control study in which each case was matched one to one to an HIV-infected control according to sex, age, CD4 cell count, viraemia and medication use. CFTR mutations and SPINK-1 polymorphisms were studied using polymerase chain reaction techniques.
  
  
  RESULTS
  Fifty-one HIV-positive patients with hyperamylasemia were detected among 1152 participants in the toxicity study (4.4%). There were 13 carriers of CFTR and SPINK-1 mutations (12.7%). Amylase levels were 316 +/- 130 U/l for the group with mutations, and 135 +/- 18 U/l for non-carriers (P = 0.79). However, among patients with hyperamylasemia, those with CFTR or SPINK-1 mutations had 648 +/- 216 U/l amylase levels compared with 232 +/- 28 U/l for those without (P = 0.025). Ten patients had acute pancreatitis, four of whom had CFTR mutations or SPINK-1 polymorphisms (40%) compared with seven of the control patients (14%) (P = 0.01).
  
  
  CONCLUSIONS
  CFTR mutations and SPINK-1 polymorphisms are frequent among HIV-positive patients suffering from acute pancreatitis. These mutations may increase the susceptibility to pancreatitis when exposed to environmental risk factors.
authors.affiliation: Division of Gastroenterology, and Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Felley
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morris
authors.forename: Ambroise
authors.initials: A
authors.lastname: Wonkam
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Markus
authors.initials: M
authors.lastname: Flepp
authors.forename: Katja
authors.initials: K
authors.lastname: Wolf
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Frossard
mesh_terms: D000208:Acute Disease; D000328:Adult; D000681:Amylases / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010195:Pancreatitis / Q000201:enzymology / Q000821:virology*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: C505032:CFTR protein, human; D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D000681:Amylases