The role of CFTR and SPINK-1 mutations in pancreatic disorders in HIV-positive patients: a case-control study

AIDS. 2004 Jul 23;18(11):1521-7. doi: 10.1097/01.aids.0000131356.52457.7a.

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.

Method: 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).

Conclusion: 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.

MeSH terms

  • Acute Disease
  • Adult
  • Amylases / blood
  • Carrier Proteins / genetics*
  • Case-Control Studies
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Female
  • HIV Infections / enzymology
  • HIV Infections / genetics*
  • Humans
  • Male
  • Mutation / genetics*
  • Pancreatitis / enzymology
  • Pancreatitis / virology*
  • Polymorphism, Genetic
  • Risk Factors
  • Trypsin Inhibitor, Kazal Pancreatic

Substances

  • CFTR protein, human
  • Carrier Proteins
  • SPINK1 protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Trypsin Inhibitor, Kazal Pancreatic
  • Amylases