Analysis of tumor necrosis factor-α, transforming growth factor-β1, interleukin-10, and interferon-γ polymorphisms in patients with alcoholic chronic pancreatitis

Schneider, Alexander; Barmada, M.Michael; Slivka, Adam; Martin, John A.; Whitcomb, David C.

doi:10.1016/j.alcohol.2003.09.006

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Volume 32, Issue 1 , Pages 19-24, January 2004

Analysis of tumor necrosis factor-α, transforming growth factor-β₁, interleukin-10, and interferon-γ polymorphisms in patients with alcoholic chronic pancreatitis

Alexander Schneider
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
M.Michael Barmada
- Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA
Adam Slivka
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
John A. Martin
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
David C. Whitcomb
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA 15213, USA
- VA Pittsburgh Healthcare System, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Center for Genomic Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Corresponding author. University of Pittsburgh, 571 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15213, USA. Tel.: +1-412-648-9604; fax: +1-412-383-7236.

Received 26 February 2003; received in revised form 21 August 2003; accepted 30 September 2003.

Editor: T.R. Jerrells

Abstract

The pathophysiologic mechanisms underlying alcoholic chronic pancreatitis are poorly understood. Cytokines participate in the immunologic progression of acute and chronic pancreatitis and may play an important role in the development of pancreatic fibrosis. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-α) gene at positions −308 and −238; in the transforming growth factor-beta 1 (TGF-β₁) gene at positions −509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position −1082; and in the intron 1 of the interferon-gamma (IFN-γ) gene at position +874 are associated with alcoholic chronic pancreatitis. We investigated 42 patients with alcoholic chronic pancreatitis. We studied 94 control subjects for the TNF-α polymorphisms and 73 control subjects for the remaining polymorphisms. Mutation analysis was performed by direct DNA sequencing or by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The genotype frequencies were similar between patients and control subjects for all investigated cytokine polymorphisms (P>.05). We did not find an association between the different genotypes and the clinical course of the disease. Therefore, we assume that these genetic variants do not play a dominant role in alcoholic chronic pancreatitis.