TGF-β1 Gene Polymorphisms Research Articles

Transforming growth factor-β1 (C509T, G800A, and T869C) gene polymorphisms and risk of ischemic stroke in North Indian population: A hospital-based case-control study.

Background:Transforming growth factor-beta 1 (TGF-β1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population.Methods:A total of 250 IS patients and 250 age- and sex-matched controls were studied. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of IS. Genotyping was performed using SNaPshot method.Results:Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary lifestyle, and low socioeconomic status were found to be associated with the risk of IS. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium in the IS and control groups. Adjusted conditional logistic regression analysis showed a significant association of TGF-β1 C509T (odds ratio [OR], 2.1; 95% CI; 1.2–3.8; P = 0.006), G800A (OR, 4.4; 95% CI; 2.1–9.3; P < 0.001) and T869C (OR, 2.6; 95% CI; 1.5–4.5; P = 0.001) with the risk of IS under dominant model. Haplotype analysis showed that C509-A800-T869 and T509-G800-C869 haplotypes were significantly associated with the increased risk of IS. C509T and T869C were in strong linkage disequilibrium (D' =0.51, r2 = 0.23).Conclusion:Our results suggest that TGF-β1 polymorphisms and their haplotypes are significantly associated with the risk of IS in North Indian population.

Genetic polymorphisms of interleukin-10 and transforming growth factor-β1 and antituberculosis drugs-induced liver injury

Purpose: Drug-induced liver injury is one of the serious adverse reactions resulting in severe morbidity and discontinuation of med ications. Previously, IL-10 gene polymorphism has been reported to be associated with diclofenac-induced hepatitis. In this study, we aimed to investigate the associations between genetic polymorphisms of immune-regulating cytokines (IL-10 and TGF-β1) with antituberculosis drugs (ATD)-induced liver injury. Methods: We enrolled 80 patients with ATD-induced liver injury and 238 ATD-tolerant controls. Two single nucleotide polymor phisms (SNP) of IL-10 (-1082A>G, rs1800896; -819T>C, rs1800871) and one promoter SNP of TGF-β1 gene (-509C>T, rs1800469) were genotyped in both groups. Genotype frequencies of these SNPs were compared between case and control groups. Results: In 2 promoter SNPs of IL-10 gene, there was no significant difference of genotype frequencies between patients with ATD-induced liver injury and controls. In addition, the genotype frequency of TGF-β1 -509C>T SNP in ATD-induced liver injury patients were not different from those of controls. Conclusion: In conclusion, there was no significant association between IL-10 and TGF-β1 gene polymorphisms and ATD-induced liver injury. These findings suggest that IL-10 and TGF-β1 do not play important role in the development of ATD-induced liver injury. (Allergy Asthma Respir Dis 2017:5:41-46)

Influence of IL-6, IL-8, and TGF-β1 gene polymorphisms on the risk of human papillomavirus-infection in women from Pernambuco, Brazil.

Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil. We analysed 108 healthy uninfected women (HC) and 108 HPV-positive women with cervical lesions. Genetic polymorphisms were assessed using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism. Comparison of the distribution of the genotypic and allelic frequencies of the IL-18 +396 T>G polymorphism between HPV infected woman an uninfected controls showed that the GG genotype and G allele were both more frequent in the HC group, and were associated with protection from HPV infection (p = 0.0015; OR = 0.29 CI95% = 0.13-0.61; p = 0.0005; OR = 0.45 CI95% 0.29-0.7, respectively). Individuals from the control group could have previously had HPV infection that was spontaneously eliminated; however, it was undetectable at the time of sample collection. Based on our findings, we hypothesize that the IL-8 +396 G>T polymorphism could interfere with susceptibility to HPV infection, by modulating the ability of immune system to fight the virus.

Single nucleotide polymorphisms in the TGF-β1 gene are associated with polycystic ovary syndrome susceptibility and characteristics: a study in Korean women.

Although many hypotheses regarding the pathogenesis of polycystic ovary syndrome (PCOS) have been generated, genetic studies have not identified specific genes that play a role in PCOS etiopathogenesis. This study aimed to investigate the relationship between TGF-β1 gene polymorphism and PCOS in Koreans. A total of 51 Korean women with PCOS and 69 healthy women were enrolled. We analyzed 4 single nucleotide polymorphisms (SNPs) of the TGF-β1 gene (rs11466313, rs1800469, rs2317130, and rs4803457). We also analyzed laboratory measurements, such as free testosterone, glucose, and cholesterol. The frequencies of rs1800469T allele negativity, rs4803457T allele negativity, the rs1800469CC genotype, and the rs4803457CC genotype showed positive associations with PCOS (P = 0.003, P = 0.027, P = 0.009, and P=0.031, respectively), whereas the haplotypes rs1800469C-rs4803457T and rs1800469T-rs4803457T showed negative associations with PCOS. A strong protective effect of the "rs1800469CT-rs4803457TT" combination (OR = 0.09) and a strong risk effect of "rs1800469CC-rs4803457CC" (OR = 6.23) for PCOS were observed. The rs1800469C/T and rs2317130C/T SNPs exhibited associations with several laboratory measurements with various levels of significance. The results demonstrated an association of TGF-β1 gene polymorphisms with the development and/or characteristics of PCOS in the Korean population.

The Effect of TGFB1 and CD14 Gene Polymorphisms on the Clinical Findings of Cystic Fibrosis in Turkish Patients

The Effect of TGFB1 and CD14 Gene Polymorphisms on the Clinical Findings of Cystic Fibrosis in Turkish Patients

Association Between the Transforming Growth Factor Beta 1 Gene Polymorphisms and Turkish Patients with Nonsyndromic Cleft Lip With/Without Cleft Palate.

To examine transforming growth factor beta 1 (TGFβ1) gene polymorphisms in Turkish patients with nonsyndromic cleft lip with/without cleft palate (nsCL/P). A total of 205 Turkish subjects were included; 80 nsCL/P patients and 125 unrelated control individuals. Analysis of gene polymorphisms was carried out by polymerase chain reaction and DNA sequencing. We found the substitution of a proline by a leucine at codon 10 (Pro10Leu) and the substitution of an arginine by a proline at codon 25 (Arg25Pro) in exon 1 of the TGFβ1 gene in nsCL/P patients. This is the first report investigating prevalence of TGFβ1 polymorphisms in Turkish patients with nsCL/P.

The Effect of TGFB1 and CD14 Gene Polymorphisms on the Clinical Findings of Cystic Fibrosis in Turkish Patients

The Effect of TGFB1 and CD14 Gene Polymorphisms on the Clinical Findings of Cystic Fibrosis in Turkish Patients

Effects of Two Common Promoter Polymorphisms of Transforming Growth Factor-β1 on Breast Cancer Risks in Ahvaz, West South of Iran.

BackgroundTransforming growth factor-β1 (TGF-β1) has a critical role in breast cancer initiation and progression.ObjectivesWe have investigated the possible differences in two promoter polymorphisms (-509C/T and -800G/A) of TGF-β1 gene between breast cancer cases and controls.Patients and MethodsA total of 100 patients with confirmed breast cancer and 100 subjects without breast cancer was selected. Two promoter polymorphisms (-509C/T and -800G/A) of TGF-β1 gene were genotyped using PCR-based restriction fragment length polymorphism (RFLP) method.ResultsThe allele frequencies were 63% for C allele and 37% for T allele of SNP -509C/T and 66% for G allele and 34% for A allele of SNP -800G/A. Although no significant difference has observed between two groups, according to the genotype distribution, However, the TT genotype of -509 and AA genotype of -800 was significantly associated with breast cancer risk [odds ratio (OR) = 2.409; 95% confidence interval (CI) = 1.087 - 5.337, P = 0.030; and OR = 2.383; CI = 1.039 - 5.40, P = 0.040, respectively]. In addition, a multinomial logistic regression model shown, homozygous of -800 G/A (OR = 0.570; 95% CI = 0.362 - 0.896, P = 0.015); and HDL-C (OR = 0.935; 95% CI = 0.906 - 0.965, P < 0.001) were the selected variables associated with the presence of breast cancer. Haplotype analysis has shown no significant association between TGF-β1 haplotypes and breast cancer risk.ConclusionsOur results indicated that among two promoter polymorphisms of the TGF-β1gene, -800G/A compared to -509C/T is more associated with breast cancer.

Brain Derived Neurotrophic Factor Modification of Epileptiform Burst Discharges in a Temporal Lobe Epilepsy Model.

Introduction:Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS.Methods:Male Wistar rats were divided into sham (receiving phosphate buffered saline within dorsal hippocampus), pilocarpine (epileptic model of TLE), single injection BDNF (epileptic rats which received single high dose of BDBF within dorsal hippocampus), and multiple injections BDNF (epileptic rats which received BDNF in days 10, 11, 12, and 13 after induction of TLE) groups. Their electrocorticogram was recorded and amplitude, frequency, and duration of spikes were evaluated.Results:Amplitude and frequency of epileptiform burst discharges were significantly decreased in animals treated with BDNF compared to pilocarpine group.Conclusion:Our findings suggested that BDNF may modulate the epileptic activity in the animal model of TLE. In addition, it may have therapeutic effect for epilepsy. More studies are necessary to clarify the exact mechanisms of BDNF effects.

Association of Transforming Growth Factor Beta-1-509C/T Gene Polymorphism with Ischemic Stroke: A Meta Analysis.

Introduction:Transforming Growth Factor-Beta 1 (TGF-β1) is a pleiotropic cytokine with potent anti-inflammatory property, which has been considered as an essential risk factor in the inflammatory process of Ischemic Stroke (IS), by involving in the pathophysiological progression of hypertension, atherosclerosis, and lipid metabolisms. -509C/T TGF-β1 gene polymorphism has been found to be associated with the risk of IS. The aim of this meta-analysis was to provide a relatively comprehensive account of the relation between -509C/T gene polymorphisms of TGF-β1 and susceptibility to IS.Methods:A review of literature for eligible genetic association Studies published before October 20, 2014 was conducted in the PubMed, EMBASE, Google Scholar and Trip database. The strength of association was calculated by pooled odds ratios (ORs) with 95% confidence intervals using RevMan 5.3 software. Heterogeneity was examined using Higgins I-squared, Tau-squared, and Chi-squared tests.Results:A total of 2 studies involving 614 cases and 617 controls were found. The overall estimates did not show any significant relation between TGF-β1-509C/T polymorphism and risk of IS under dominant (CC+CT vs. TT: OR=1.01, 95%CI=0.31 to 3.26; P=0.99), recessive (CC vs. CT+TT: OR=0.94, 95%CI=0.47 to 1.90; P=0.87), and allelic models (T vs. C: OR=1.06, 95%CI=0.55 to 2.04; P=0.86).Conclusion:This meta-analysis showed that TGF-β1-509C/T gene polymorphism has no significant association with the susceptibility of IS. Further well-designed prospective studies with larger sample size are needed to confirm these findings.

Impact of TGF-β1 Gene Polymorphism (rs1800469) on Treatment Response to Pegylated Interferon/Ribavirin in Iranian Patients with Hepatitis C.

Hepatitis C virus as a major cause of chronic liver disease affects more than 170 million people worldwide. Recent studies have claimed that single nucleotide polymorphisms (SNPs) for the transforming growth factor-β1 (TGF-β1) gene were strongly associated with the antiviral treatment response. Thus, the present study aimed at the determination of distribution of the rs1800469 (C/T) polymorphism among Iranian with chronic hepatitis C. A total of 165 blood samples including 68 SVR positive and 21 non-responder samples from individuals suffering chronic hepatitis C and also 76 healthy individual controls were analyzed in this cross-sectional study. DNA was isolated from the samples using a DNA extraction standard kit. Then the frequency of the polymorphism was analyzed using PCR-RFLP method. Eventually, the products of interest were detected on 2.5% agarose gel electrophoresis. The distribution of the C/T polymorphism between healthy individuals and patients were obtained as TT: 22.4%, TC: 46%, CC: 31.6%, and TT: 19.1%, TC: 48.3%, CC: 32.6%, respectively. Furthermore, the CC genotype was identified in 20 patients of whom 68 achieved SVR, while the CT heterozygous was found in 43 patients and SVR was achieved in 38. Finally, the TT was detected in 17 patients, and 7 patients did not achieve SVR. We observed a significant difference of C allele frequency with SVR as compared to the T allele among patients (p = 0.064). On the other hand, there is no correlation between the polymorphism and susceptibility to HCV infection. However, further studies with more samples seem to be necessary.

Association of transforming growth factor-β1 gene C509T, G800A and T869C polymorphisms with intracerebral hemorrhage in North Indian Population: a case-control study.

Transforming growth factor-β1 (TGF-β1) is a multifunctional pro-inflammatory cytokine involved in inflammation and pathogenesis of cerebrovascular disease. As per our knowledge, there is no published study investigating the association between variations within the TGF-β1 gene polymorphisms and risk of intracerebral hemorrhage (ICH). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A and T869C) polymorphisms, and their haplotypes with the risk of ICH in North Indian population. 100 ICH patients and 100 age- and sex-matched controls were studied. Genotyping was performed using SNaPshot method. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of ICH. Hypertension, diabetes, dyslipidemia, low socioeconomic status, smoking, physical activity were found to be associated with the risk of ICH. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium (HWE) in the ICH and control group. Adjusted conditional logistic regression analysis showed an independent association of TGF-β1 G800A (OR 9.07; 95% CI 2.3-35.6; P = 0.002) and T869C (OR 5.1; 95 % CI 1.9-13.2; P = 0.001) with the risk of ICH under dominant model. Haplotype analysis showed that C509-G800-C869 and C509-A800-C869 haplotypes were significantly associated with the increased risk of ICH. C509T and T869C were in strong linkage disequilibrium (D' = 0.53, r(2) = 0.23). Our results suggest that TGF-β1 (G800A, T869C) gene polymorphisms and their haplotypes are significantly associated with the risk of ICH in North Indian population. Further prospective studies with large sample size are required for independent validation. Our findings could be helpful in identifying individuals at increased risk for developing ICH.

Association of transforming growth factor-β1 gene C509T, G800A and T869C polymorphisms with ischemic stroke in North Indian population: a case–control study

Background: Stroke is a multi-factorial polygenic disease which is influenced by both genetic and environmental factors. Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine involved in inflammation and pathogenesis of atherosclerosis. There is limited information on the relation between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS).Objective: The aim of this present study is to investigate the association of the TGF-β1 gene (C-509 T, G800A and T869C) polymorphisms with the risk of IS in North Indian population.Methods: In a hospital based case control study, patients with IS and control subjects were recruited from inward and outward of Neurology department, All India Institute of Medical Sciences, New Delhi. Genotyping was performed by using SnaPshot Method. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Frequency distributions of genotypes and alleles were compared between cases and controls using multivariate logistic regression.Results: In this study, 250 IS patients and 250 age-and sex-matched control subjects were recruited. Mean age of cases and controls were 52.8 ± 12.5 and 50.9 ± 12.7 years respectively. Multivariate logistic regression analysis showed significant association between TGF-β1 gene polymorphisms with the risk of IS; for C509T (Odds ratio [OR], 2.19; 95% CI, 1.25 to 3.83), for G800A (OR, 4.43; 95% CI, 2.10 to 9.32) and for T869C (OR, 2.63; 95% CI, 1.52 to 4.54) under dominant model of inheritance.Conclusions: Our findings suggest that TGF-β1 gene polymorphisms are significantly associated with the risk of IS in a North Indian population. Background: Stroke is a multi-factorial polygenic disease which is influenced by both genetic and environmental factors. Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine involved in inflammation and pathogenesis of atherosclerosis. There is limited information on the relation between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS). Objective: The aim of this present study is to investigate the association of the TGF-β1 gene (C-509 T, G800A and T869C) polymorphisms with the risk of IS in North Indian population. Methods: In a hospital based case control study, patients with IS and control subjects were recruited from inward and outward of Neurology department, All India Institute of Medical Sciences, New Delhi. Genotyping was performed by using SnaPshot Method. Stroke was classified using Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Frequency distributions of genotypes and alleles were compared between cases and controls using multivariate logistic regression. Results: In this study, 250 IS patients and 250 age-and sex-matched control subjects were recruited. Mean age of cases and controls were 52.8 ± 12.5 and 50.9 ± 12.7 years respectively. Multivariate logistic regression analysis showed significant association between TGF-β1 gene polymorphisms with the risk of IS; for C509T (Odds ratio [OR], 2.19; 95% CI, 1.25 to 3.83), for G800A (OR, 4.43; 95% CI, 2.10 to 9.32) and for T869C (OR, 2.63; 95% CI, 1.52 to 4.54) under dominant model of inheritance. Conclusions: Our findings suggest that TGF-β1 gene polymorphisms are significantly associated with the risk of IS in a North Indian population.

TGF-β1 gene − 509C > T promoter polymorphism modulates TGF-β1 levels in hepatitis E patients

Elevated levels of transforming growth factor-β1 (TGF-β1) and its positive correlation with Foxp3 expression in hepatitis E patients have indicated involvement of TGF-β1 in hepatitis E pathogenesis. The current study determined polymorphisms in TGF-β1 gene, plasma TGF-β1 levels and T effector (Teff) cell proliferation and explored their association in a case control study. Polymorphisms in three selected sites (−509C>T, +869T>C and +915G>C) of TGF-β1 gene by PCR & restriction fragment length polymorphism methods, plasma TGF-β1 quantitation by ELISA and Teff (CD4+CD25−) cell proliferation by CFSE method were carried out in 277 hepatitis E patients (HE) with self-limiting infection and 233 ethnically matched healthy controls (HCs) from western India. Frequency of CT genotype of −509C>T site was significantly higher in hepatitis E patients compared to healthy controls (p=0.017; OR 1.53, 95% CI 1.07–2.17). Plasma TGF-β1 levels were significantly higher in HE compared to HCs. TGF-β1 level of patient group having CT genotype of −509C>T site was significantly higher compared to those having CC or TT genotypes. Teff cell proliferation was negatively correlated with plasma TGF-β1 levels in HE patients (r=−0.568; p=0.014). Influence of TGF-β1 promoter (−509C>T) polymorphism on plasma TGF-β1 levels and inverse correlation of Teff cell proliferation with plasma TGF-β1 levels in self-limiting hepatitis E patients suggest key role of TGF-β1 in augmentation of reported T regulatory cell mediated pathogenesis in hepatitis E.

Arg25Pro (c.915G>C) polymorphism of transforming growth factor β1 gene suggests an association with increased risk for Hashimoto's thyroiditis

BackgroundThe etiopathogenesis of Hashimoto's thyroiditis (HT) — has not been clearly elucidated although the role of chronic inflammation, endothelial dysfunction, and imbalance between pro- and anti-inflammatory cytokines has been established. Transforming growth factor β1 (TGFβ1) is required to maintain immune homeostasis, and is implicated in lymphocyte infiltration, production of autoantibodies and thyrocyte destruction seen in patients with HT. AimThe aim of the present study was to investigate the possible association of Leu10Pro (c.869T>C) and Arg25Pro (c.915G>C) single nucleotide polymorphisms (SNPs) of TGFβ1 gene with the occurrence of HT. MethodsWe analyzed the genotype and allele frequencies of polymorphisms at codon 10 and 25 in 178 patients who had been diagnosed as having HT and 197 healthy controls using PCR-restriction fragment length polymorphism (RFLP). ResultsThere was no notable risk for HT afflicted by Leu10Pro (c.869T>C) polymorphism of TGFβ1 gene. However, there was a significant increase of Arg25Pro (c.915G>C) C allele frequency in patients with HT compared with healthy controls (p=0.003, OR=1.87, 95% CI=1.23–2.84). Moreover, heterozygous (CG) subjects had a 2.53-fold increased risk for developing HT with respect to wild (GG) homozygotes (p<0.001, 95% CI=1.57–4.05). TSH levels in CG heterozygous patients were increased in comparison with wild homozygotes (p=0.006). ConclusionThis study indicates that the Arg25Pro (c.915G>C) polymorphism of TGFβ1 gene may be related to increased risk for HT.

A Preliminary Study on Racial Differences in HMOX1, NFE2L2, and TGFβ1 Gene Polymorphisms and Radiation-Induced Late Normal Tissue Toxicity

This study tested whether racial differences in genetic polymorphisms of 4 genes involved in wound repair and response to radiation can be used to predict the occurrence of normal tissue late effects of radiation therapy and indicate potential therapeutic targets. This prospective study examined genetic polymorphisms that modulate the expression of 4 genes involved in inflammation and fibrosis and response to radiation (HMOX1, NFE2L2, NOS3, and TGFβ1). DNA from blood samples of 179 patients (∼ 80% breast and head and neck) collected at the time of diagnosis by their radiation oncologist as exhibiting late normal tissue toxicity was used for the analysis. Patient demographics were as follows: 56% white, 43% African American, 1% other. Allelic frequencies of the different polymorphisms of the participants were compared with those of the general American population stratified by race. Twenty-six additional patients treated with radiation, but without toxicity at 3 months or later after therapy, were also analyzed. Increased frequency of a long GT repeat in the HMOX1 promoter was associated with late effects in both African American and white populations. The single nucleotide polymorphisms (SNP) rs1800469 in the TGFβ1 promoter and the rs6721961 SNP in the NFE2L2 promoter were also found to significantly associate with late effects in African Americans but not whites. A combined analysis of these polymorphisms revealed that >90% of African American patients with late effects had at least 1 of these minor alleles, and 58% had 2 or more. No statistical significance was found relating the studied NOS3 polymorphisms and normal tissue toxicity. These results support a strong association between wound repair and late toxicities of radiation. The presence of these genetic risk factors can vary significantly among different ethnic groups, as demonstrated for some of the SNPs. Future studies should account for the possibility of such ethnic heterogeneity in the late toxicities of radiation.

C.29C>T polymorphism in the transforming growth factor-β1 (TGFB1) gene correlates with increased risk of urinary bladder cancer

TGF-β1 is a pleiotropic cytokine, which plays a dual role in tumor development. In the early stages, it inhibits the growth of tumor while in the late stages of carcinoma, it promotes tumor growth. The purpose of this study was to analyze the distribution of the TGFB1 gene polymorphisms between cases and controls so as to assess their correlation with bladder cancer risk. This study included 237 cases of urinary bladder cancer and 290 age matched controls from the same ethnic background. Three polymorphisms in the TGFB1 gene, c.29C>T (rs-1800470), c.74G>C (rs-1800471) and +140A>G (rs-13447341), were analyzed by direct DNA sequencing. Statistical analyses revealed no significant differences in the demographical data, except that the frequencies of smokers and non-vegetarians were higher in the cases. Eighty percent of the bladder cancer patients had superficial transitional cell carcinoma, and 53.16% and 26.31% of the patients were in grade I and grade II, respectively. We found that c.29C>T substitution increased the risk of bladder cancer significantly and recessive model of analysis was the best fitted model (p=0.004; OR=1.72 95% CI 1.18–2.50). A significantly higher risk in the recessive form was also suggested by co-dominant analysis showing that the homozygous form (TT) was a significant risk factor in comparison to CC and CT genotypes. The other two polymorphisms, c.74G>C (p=0.18, OR=0.67 95% CI 0.37–1.21) and +140A>G (p=0.416, OR=0.77 95% CI 0.41–1.45) did not affect the risk of urinary bladder cancer. In conclusion, we found that the TGFB1 c.29C>T substitution increases the risk of bladder cancer significantly while c.74G>C and +140A>G polymorphisms do not affect the risk.

Impact of TGF-β1 -509C/T and 869T/C polymorphisms on glioma risk and patient prognosis.

Transforming growth factor beta (TGF-β) plays an important role in carcinogenesis. Two polymorphisms in the TGF-β1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancers. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study, we investigated the relevance of these TGF-β1 polymorphism in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). The influence of TGF-β1 -509C/T and 869T/C polymorphisms on glioma patient survival was evaluated by a Cox regression model adjusted for patients' age and sex and represented in Kaplan-Meier curves. Our results demonstrated that TGF-β1 gene polymorphisms -509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous -509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC + CT genotypes (OR, 2.41; 95 % CI, 1.06-5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT + TC genotypes (OR, 2.62; 95 % CI, 1.11-6.17; p = 0.027). In conclusion, this study suggests that TGF-β1 -509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas but may be relevant prognostic biomarkers in GBM patients.

Sex differences in TGFB-β signaling with respect to age of onset and cognitive functioning in schizophrenia.

There are studies showing that gene polymorphisms within the transforming growth factor-β (TGF-β) signaling constitute schizophrenia risk variants. However, the association between TGFB1 gene polymorphisms (+869T/C and +915G/C), TGF-β level with schizophrenia course, and its symptomatology together with cognitive functioning has not been investigated so far. We included 151 patients with schizophrenia and 279 healthy controls. Cognitive functioning was assessed using Rey Auditory Verbal Learning Test, Trail Making Test (TMT)-A and TMT-B, Verbal Fluency task, Stroop test, as well as selected subtests from the Wechsler Adults Intelligence Scale – Revised, Polish adaptation (WAIS-R-Pl): Digit Symbol Coding, Digit Span Forward and Backward, and Similarities. Additionally, serum TGF-β levels were measured in 88 schizophrenia patients and 88 healthy controls. Serum TGF-β level was significantly higher among patients with schizophrenia in comparison with healthy controls; however, the studied polymorphisms were not associated with TGF-β level in schizophrenia patients. Subjects carrying the +869T allele performed significantly worse in comparison with +869CC homozygotes on Stroop task, Verbal Fluency task and Digit Symbol Coding task. There was a significant difference in age of psychosis onset in female schizophrenia patients with respect to the TGFB1 +869T/C polymorphism. Additionally, adjustment for possible confounders revealed that there was a significant difference in cognitive performance on Digit Symbol Coding task with respect to the TGFB1 +869T/C polymorphism among female schizophrenia patients. Our results suggest that TGF-β signaling might be a valid link contributing to observed differences in age of onset and the level of cognitive decline between male and female schizophrenia patients.

Correlation between TGF-β1 gene 29 T > C single nucleotide polymorphism and clinicopathological characteristics of osteosarcoma.

Transforming growth factor (TGF)-β1 is the most abundant growth factor in human bone. Several polymorphisms have been described in the TGF-β1 gene. To explore the correlation between TGF-β1 gene single nucleotide polymorphism and the clinicopathological characteristics of osteosarcoma. TaqMAN PCR technique was used to detect the TGF-β1 gene polymorphism of 124 patients with osteosarcoma from last follow-up and 136 healthy controls. The difference of gender, age, and allele frequency between patient group and control group with χ (2) text were tested. The relationship between single nucleotide polymorphism and the risk of osteosarcoma with logistic regression and different survival rates of different genotypic patients with osteosarcoma through Kaplan-Meier were analyzed. There is no remarkable difference of the three genotypes in TGF-β1 gene 509C > T locus between the patient group and control group (P = 0.26). However, there are significant distributive differences in 29 T > C genotype (P = 0.04), which shows that patients carrying TT genotype have more risk to get osteosarcoma than patients carrying CC genotype (odds ratio (OR) = 2.10, 95 % confidence interval (CI) = 1.08-4.05). The percentage of T allele frequency of patient group, as 60.1 %, is larger than the control group, as 48.9 %. By comparing with patients carrying CC genotype, patients carrying TT genotype have two times risk of metastasis (OR = 2.30, 95 % CI = 1.05-5.06), and most of them are in the period of Enneking IIB (OR = 2.54, 95 % CI = 1.18-5.51). The survival analysis indicates that there is no any significant decrease when there is recurrence in patients carrying TT genotype. The morbidity and metastasis of osteosarcoma are relevant to TGF-β1 gene 29 T > C single nucleotide polymorphism.