Analysis of common transforming growth factor beta-1 gene polymorphisms in gastric and duodenal ulcer disease: Pilot study

作者：Polonikov Alexey V^*; Ivanov Vladimir P; Belugin Dmitry A; Khoroshaya Irina V; Kolchanova Inessa O; Solodilova Mariya A; Tutochkina Margarita P; Stepchenko Alexander A

来源：Journal of Gastroenterology and Hepatology, 2007, 22(4): 555-564.

DOI：10.1111/j.1440-1746.2006.04542.x

• case-control study
• gastric and duodenal ulcer disease
• genetic polymorphism
• transforming growth factor beta-1
• ulcer healing

Background and Aim: Transforming growth factor-beta 1 (TGF-beta 1) has been shown to be an important cytokine that plays a role in cell proliferation, differentiation, tissue injury repair and ulcer healing. The purpose of this pilot study was to investigate if common polymorphisms Leu10Pro, Arg25Pro and C-509T within the TGF-beta 1 gene are associated with susceptibility to gastric and duodenal ulcer disease in Russians.
Method: Blood samples from 377 unrelated patients with gastric and duodenal ulcer disease and 226 sex- and age-matched healthy controls were used to determine TGF-beta 1 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results: Leu10Pro substitution in the signal peptide of TGF-beta 1 has been found to be associated with susceptibility to gastric ulcer (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.12-2.77). A genotype combination of 10Leu/Leu x 25Arg/Arg x -509C/C was also associated with susceptibility to gastric ulcer disease (OR 1.81, P = 0.01). In addition, the frequency of a combination of genotypes 10Pro/Pro x 25Arg/Pro x -509C/T was statistically lower in patients with duodenal ulcer than in controls (OR 0.42, P = 0.05). A significant difference (P = 0.04) in the distribution of rare haplotypes of the TGF-beta 1 gene between patients with duodenal ulcer and healthy controls has been found. Polymorphism Leu10Pro was in positive linkage disequilibrium with C-509T polymorphism (coefficient D = 0.191; P < 0.0001).
Conclusions: These findings indicate that the Leu10Pro and C-509T polymorphisms may be involved in the modulation of expression of the TGF-beta 1 gene, and therefore a predisposition to peptic ulcer disease could be linked to particular alleles of this gene. In particular, a possible role of TGF-beta 1 in the pathogenesis of gastric ulcer disease is discussed.

• 出版日期2007-4