Analysis of common transforming growth factor beta-1 gene polymorphisms in gastric and duodenal ulcer disease: pilot study.
OBJECTIVE
Transforming growth factor-beta1 (TGF-beta1) 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-beta1 gene are associated with susceptibility to gastric and duodenal ulcer disease in Russians.


METHODS
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-beta1 gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).


RESULTS
Leu10Pro substitution in the signal peptide of TGF-beta1 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-beta1 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-beta1 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-beta1 in the pathogenesis of gastric ulcer disease is discussed.
Polonikov
Alexey V
AV
Medical Biology, Genetics and Ecology Department, Kursk State Medical University, Kursk, Russia. medbiol@kursknet.ru
Ivanov
Vladimir P
VP
Belugin
Dmitry A
DA
Khoroshaya
Irina V
IV
Kolchanova
Inessa O
IO
Solodilova
Mariya A
MA
Tutochkina
Margarita P
MP
Stepchenko
Alexander A
AA
D000328:Adult; D004381:Duodenal Ulcer / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D016481:Helicobacter Infections / Q000235:genetics; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013276:Stomach Ulcer / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000502:physiology
D053773:Transforming Growth Factor beta1