The role of CFTR and SPINK-1 mutations in pancreatic disorders in HIV-positive patients: a case-control study.
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.
Felley
Christian
C
Division of Gastroenterology, and Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Morris
Michael A
MA
Wonkam
Ambroise
A
Hirschel
Bernard
B
Flepp
Markus
M
Wolf
Katja
K
Furrer
Hansjakob
H
Battegay
Manuel
M
Bernasconi
Enos
E
Telenti
Amalio
A
Frossard
Jean-Louis
JL
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
C505032:CFTR protein, human; D002352:Carrier Proteins; C486642:SPINK1 protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D014359:Trypsin Inhibitor, Kazal Pancreatic; D000681:Amylases