Schneider Alexander, Barmada M Michael, Slivka Adam, Martin John A, Whitcomb David C
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Alcohol. 2004 Jan;32(1):19-24. doi: 10.1016/j.alcohol.2003.09.006.
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-alpha) gene at positions -308 and -238; in the transforming growth factor-beta 1 (TGF-beta(1)) 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-gamma) 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-alpha 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.
酒精性慢性胰腺炎潜在的病理生理机制目前仍知之甚少。细胞因子参与急性和慢性胰腺炎的免疫进展过程，并且可能在胰腺纤维化的发展中起重要作用。现已确定细胞因子基因中的功能多态性会改变细胞因子的产生。本研究的目的是确定肿瘤坏死因子-α（TNF-α）基因-308和-238位点；转化生长因子-β1（TGF-β1）基因-509、+869（密码子10）和+915（密码子25）位点；白细胞介素-10（IL-10）基因-1082位点；以及干扰素-γ（IFN-γ）基因内含子1 +874位点的功能多态性是否与酒精性慢性胰腺炎相关。我们调查了42例酒精性慢性胰腺炎患者。我们对94名对照者进行了TNF-α多态性研究，对其余多态性则研究了73名对照者。通过直接DNA测序或扩增阻滞突变系统-聚合酶链反应（ARMS-PCR）进行突变分析。在所有研究的细胞因子多态性中，患者和对照者之间的基因型频率相似（P>0.05）。我们没有发现不同基因型与疾病临床病程之间存在关联。因此，我们认为这些基因变异在酒精性慢性胰腺炎中不发挥主导作用。
