transforming-growth-factor-beta and Gallstones

Gallstone is a common biliary disorder with several risk factors. Immune responses and inflammatory cytokines are important in this disease; as a result, some cytokines can be detected in bile fluid. In this research, cytokine gene polymorphisms were studied, and their effects on gallstone formation were evaluated. On 158 gallstone patients and 254 normal subjects, by PCR- RFLP method, IL-4-C590T polymorphism and by ARMS-PCR method, IFN-γ T+874A, TNF-α-A308G, IL-6 G-174C and TGF-β T+869C variants were studied. Pathologic evaluations were done on surgical specimens. There were no significant differences in distribution of evaluated polymorphisms between patient group and normal control group (P > 0.05), except TGF-β +869T allele (P = 0.04, OR = 1.23, 95 % CI = 1-1.79) which was higher in patients with gallstone. Although the pro-inflammatory cytokines such as TNF-α and IL-6 may promote gallstone formation, in this study no significant correlation between TNF-α and IL-6 polymorphisms and gallstone formation was seen. It is taught that TGF-β may affect gallbladder cells to promote gallstone formation and higher producer TGF-β +869T allele can be a risk factor of gallstone disease, so further studies would be more elucidative

Topics: Adult; Aged; Alleles; Case-Control Studies; Cytokines; Female; Gallstones; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Transforming Growth Factor beta

Transforming growth factor betas (TGF-betas) are multifunctional polypeptides that either inhibit or stimulate cell proliferation. They mediate their functions through their signaling receptors. Clinically, hepatolithiasis has been regarded as a risk factor for cholangiocarcinoma. The aim of this study was to examine the expression of TGF-betas and their receptors in stone-containing intrahepatic bile ducts (IHD) and cholangiocarcinoma and try to predict whether hepatolithiasis has a predisposition to development of cholangiocarcinoma. Twenty-eight surgically resected specimens of stone-containing IHD and 15 specimens of cholangiocarcinoma were subjects for this study. Immunohistochemical analysis was done on three TGF-betas and their signaling receptors to check their expression in non-neoplastic and neoplastic bile ducts. No immunoreactivity of TGF-beta(1) was found in any specimens. The overexpression of TGF-beta(2) and TGF-beta(3) was found in both hepatolithiasis (93%-100%) and cholangiocarcinoma (80%) at levels significantly higher than those of normal controls (10%-20%) ( p< 0.001). The immunoreactivity of type I receptor (T beta RI) and type II receptor (T beta RII) also showed increased expression in stone-containing IHD, whereas T beta RII was absent in cholangiocarcinoma. We conclude that the overexpression of TGF-beta(2) and TGF-beta(3) and the absence of T beta RII in cholangiocarcinoma could lead to enhanced tumor cell proliferation. At the same time, the overexpression of TGF-betas and their receptors in stone-containing IHD could suggest a close relationship between hepatolithiasis and cholangiocarcinoma.

Topics: Adult; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Female; Gallstones; Humans; Male; Middle Aged; Receptors, Transforming Growth Factor beta; RNA, Messenger; RNA, Neoplasm; Transforming Growth Factor beta