Transforming growth factor-beta1, interleukin-10 and interferon-gamma cytokine polymorphisms in patients with hereditary, familial and sporadic chronic pancreatitis.
BACKGROUND
The genetic influence is undefined in about 40% of patients with hereditary and familial pancreatitis and in the majority of patients with sporadic chronic pancreatitis. The pathophysiological mechanisms underlying the progression from acute to chronic pancreatitis have not been clarified. Cytokines participate in the immunological progression of pancreatic inflammation and may play an important role in the development of pancreatic fibrosis.


OBJECTIVE
We determined whether functional polymorphisms in the transforming growth factor-beta1 gene at positions -509, +869 (codon 10) and +915 (codon 25), in the interleukin-10 gene at position -1082, and in the intron 1 of the interferon-gamma gene at position +874 are associated with hereditary, familial or sporadic pancreatitis.


METHODS
We investigated 78 patients with hereditary and familial pancreatitis and 62 patients with sporadic pancreatitis that were tested negative for cationic trypsinogen gene mutations, and 73 controls. Mutational analysis was performed by direct DNA sequencing or by amplification refractory mutational system polymerase chain reaction. We used the age at onset as marker of disease severity.


RESULTS
The genotype frequencies were similar between patients and controls for all investigated cytokine polymorphisms (p > 0.05). We did not find an association between the different genotypes and the age at onset of the disease, and we did not detect different genotype distributions in patients with morphological alterations on pancreatic imaging after a disease duration of up to 5 years.


CONCLUSIONS
These genetic variants do not play a dominant role in hereditary, familial or sporadic chronic pancreatitis.
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15101, USA.
Alexander
A
Schneider
M Michael
MM
Barmada
Adam
A
Slivka
John A
JA
Martin
David C
DC
Whitcomb
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D002908:Chronic Disease; D017931:DNA Primers; D005355:Fibrosis; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics*; D007438:Introns / Q000235:genetics; D010195:Pancreatitis / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D017931:DNA Primers; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007371:Interferon-gamma