Growth Factor-β1 Gene Polymorphisms Research Articles

The association between C509T, T869C, G915C gene polymorphisms of transforming growth factor-β1 and systemic lupus erythematosus risk: A meta-analysis.

The relationship between transforming growth factor-β1 (TGF- β1) gene polymorphisms and systemic lupus erythematosus (SLE) has been reported in many studies, but there were still controversies with regard to their conclusions. Relevant documents were retrieved from 5 electronic databases such as PubMed, Embase, Cochrane Library, Wanfang, and China national knowledge infrastructure. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to assess the relationship between TGF-β1 genetic variation and SLE. The present meta-analysis included 12 case-control studies with 1308 SLE patients and 1714 healthy controls. The results of the combined analyses showed that TGF-β1 C509T polymorphism showed no association with SLE risk (TC vs CC: OR = 1.16, 95% CI = 0.91-1.48, PHeterogeneity (PH) = 0.579; TT vs CC: OR = 1.15, 95% CI = 0.63-2.09, PH = 0.003; T vs C: OR = 1.08, 95% CI = 0.8-1.45, PH = 0.003; TC/TT vs CC: OR = 1.17, 95% CI = 0.93-1.46, PH = 0.133; and TT vs TC/CC: OR = 1.06, 95% CI = 0.64-1.76, PH = 0.004). TGF-β1 G915C and T869C polymorphisms were not linked with SLE risk. Moreover, subgroup analysis stratified by ethnicity and Hardy-Weinberg equilibrium revealed no significant correlation of TGF-β1 T869C, C509T, G915C polymorphisms with SLE risk. TGF-β1 T869C, C509T, G915C polymorphisms might not be associated with the development of SLE.

Association between genotyping of transforming growth factor Beta 1 with oxidative status in type 2 diabetic nephropathy Complications

Objectives: To assess the association between Transforming Growth Factor β1 gene polymorphism (T869C) and type 2 diabetes mellitus with and without nephropathy complications with endogenous antioxidant reduced glutathione levels in type 2 diabetic patients with/without nephropathy complications of Kerbala province: Iraq. Methods: A case-control study was performed at which 100 patients with diabetic nephropathy, 100 patients with only type 2 diabetic and another 100 apparently healthy individuals as control were recruited. Fasting blood glucose, HbA1c%, urea, creatinine and glutathione were measured by spectrophotometric methods using enzymatic procedures. Transforming growth factor β1 gene was genotyped for the T>C (T869C) SNP by PCR-ARMS technique. Results: The genotype and allele frequencies of TGFβ1 gene polymorphism in type 2 diabetes mellitus, type 2 diabetic nephropathy, and control were examined. The transforming growth factor β1 (T869C) C allele, TC and TC + CC genotypes were significantly higher in patients; the T allele and TT genotype were significantly higher in controls (P ≤ 0.001). Glutathione give also a significant result in diabetic patients with and without nephropathy in when compared with controls. Conclusion: The observed data indicated that TGFβ1 (T869C) codon 10, allele C, and C allele-containing genotypes may be susceptible, and the T allele / TT genotype may be protective factors for type 2diabetic nephropathy complications. The results of glutathione showed that it may be one of the causes of presence high oxidants compounds, which is lead to the damage and destruction of mutations in the DNA of the cell.

Association of Transforming Growth Factor β1 Gene Polymorphisms and Inflammatory Factor Levels with Susceptibility to Sepsis.

Objective: To study the association of transforming growth factor β1 (TGF-β1) gene single nucleotide polymorphisms (SNPs) and plasma TGF-β1 levels with susceptibility to sepsis. Methods: The genotypes of the TGF-β1 gene rs1800469, rs1800468, rs1800470, and rs1800471 loci in 285 sepsis patients (119 patients with severe sepsis and 166 patients with mild sepsis) and 285 healthy individuals (control group) were analyzed through Sanger sequencing. Enzyme-linked immunosorbent assay was used to detect the levels of plasma inflammatory factors. Results: The TGF-β1 gene SNP rs1800469 C allele was 0.56 times lower than the T allele in terms of risk of susceptibility to sepsis (95% confidence interval [CI]: 0.43-0.72, p < 0.01). Carriers of the A allele at the rs1800468 locus of the TGF-β1 were 2.82 times more susceptible to sepsis than those with the G allele (95% CI: 1.62-4.91, p < 0.01). The T allele at the rs1800470 locus of TGF-β1 produced a lower risk of sepsis than those with the C allele (odds ratio [OR] = 0.74, 95% CI: 0.57-0.94, p = 0.02). The risk of susceptibility to sepsis in the TGF-β1 rs1800471 locus G allele was 3.54 times higher than that of C allele (95% CI: 2.14-5.86, p < 0.01). The TGF-β1 gene rs1800469 T > C and rs1800470 C > T were associated with mild sepsis, whereas rs1800468 G > A and rs1800471 C > G were associated with severe sepsis (p < 0.01). The TGF-β1 gene rs1800469 T > C and rs1800470 C > T were associated with lower plasma TGF-β1 levels, whereas rs1800468 G > A and rs1800471 C > G were associated with higher TGF-β1 levels (p < 0.05). Conclusion: The alleles T > C of rs1800469 and C > T of rs1800470 of the TGF-β1 gene were associated with lower plasma TGF-β1 levels and a reduced risk of sepsis susceptibility, whereas the alleles rs1800468 G > A and rs1800471 C > G were associated with higher TGF-β1 levels and risk of susceptibility to sepsis.

Transforming growth factor-β1 gene polymorphism as a potential risk factor in Turkish patients with laryngeal squamous cell carcinoma.

Laryngeal cancer is the most common head-and-neck malignancies with more than 20% of all cases. The vast majority of tumors are squamous cell carcinoma (SCC). Several genes encoding different cytokines may play crucial roles in host susceptibility to cancer because cytokine production capacity varies among individuals and depends on cytokine gene polymorphisms. The association between cytokine gene polymorphisms with primary laryngeal SCC was investigated. DNA samples were obtained from a Turkish population of eighty patients with primary cancer and fifty healthy controls. All genotyping (interferon-gamma, transforming growth factor-β1 [TGF-β1], tumor necrosis factor-alpha [TNF-α], interleukin [IL]-6, and IL-10) experiments were performed using polymerase chain reaction sequence-specific primers. When compared to the healthy controls, the frequencies of TGF-β1 codon 25 (rs1800471) GC genotype and 25 C allele were significantly more common in the patient group. These results suggest that TGF-β1 gene polymorphisms may affect host susceptibility to laryngeal cancer.

Role of Transforming Growth Factor-β1 (T29C) Gene Polymorphism in Hepatic Stellate Cell Activation and Invasion and Susceptibility to Hepatitis B, C Infection in an Iraqi Patients

The interindividual varieties in the limit of changing development factor-β1 (TGF-β1) generation have been credited to hereditary polymorphisms in TGF-β1 quality. Changing development factor-beta 1 (TGFβ1) is a powerful suppressive cytokine that adds to ceaseless hepatitis B (CHB) disease. Abberations in TGFβ1 generation among people have been ascribed to TGFβ1 hereditary polymorphisms. We analyzed whether three putative polymorphisms in TGFβ1 (- 509 C/T (rs1800469), +869 C/T (rs1800470), and +11929 C/T (rs1800472)) square measure connected with CHB illness during a South-Eastern Iranian people.Methods:A total of 203 subjects with hepatitis infection (94 patients with hepatitis B virus infection and 109 patients with hepatitis C virus infection) whom admitted to Margan hospital, Center of liver diseases and gastrointestinal system were enrolled in the study. Allele specific (AS)-PCR, methods were used for assessing polymorphism of IL-10. Patients included (130 males and 73 females), with an age range (HBV: 44.6 ± 8.2), (HCV: 45.3±13.3) and (Control: 49.2 ± 9.04) years. The practical side of this study was done during the period from October 2017 to March 2018.Methods:A total of 203 subjects with hepatitis infection (94 patients with hepatitis B virus infection and 109 patients with hepatitis C virus infection) whom admitted to Margan hospital, Center of liver diseases and gastrointestinal system were enrolled in the study. Patients included (130 males and 73 females), with an age range (HBV: 44.6 ± 8.2), (HCV: 45.3±13.3) and (Con trol: 49.2 ± 9.04) years. The practical side of this study was done during the period from October 2017 to March 2018. As pathogenesis of HBV and HCV has a hereditary foundation, this primer investigation was intended to evaluate the effect of TGF-β1 (T29C) on the helplessness of Iraqi to HBV and HCV disease. Genotyping was performed utilizing single stranded polymorphism-polymerase chain response (SSP-PCR). Results: TGF-β1 T29Cgenetic polymorphism related to hepatitis B and C virus infection; revealed that the Genotype frequency of polymorphisms of (TGF) gene in Hepatitis B, C and Control, it was revealed that TC allele was higher than others 56.10% in control, 54.26% in HBV and 55.96% in HCV respectively. Results of Allele frequency showed that T allele was higher than C (69.51% in control, 57.98% HBV and 61.01% HCV).

Retraction: Role of Transforming Growth Factor-β1 (T29C) Gene Polymorphism in Hepatic Stellate Cell Activation and Invasion and Susceptibility to Hepatitis B, C Infection in an Iraqi Patients (J. Phys.: Conf. Ser. 1294 062012)

This article has been retracted by IOP Publishing following an allegation that the work contains tortured phrases [1]. IOP Publishing has investigated and agrees the article contains a number of nonsensical phrases that feature throughout the paper, to the extent that the article makes very little sense. This casts serious doubt over the legitimacy of the article and/or expertise of the authors in this topic. It suggests the article may have been created at least partly by artificial intelligence or translation software. The authors of the article have been given opportunity to present evidence that they were the original and genuine creators of the work, however at the time of publication of this notice, IOP Publishing has not received any response. IOP Publishing has analysed the article and agrees there are enough indicators to cause serious doubts over the legitimacy of the work and agree this article should be retracted. The authors are encouraged to contact IOP Publishing Limited if they have any comments on this retraction. Further to this, an allegation exists [2] that raises concerns over the originality of the work. IOP Publishing wishes to credit PubPeer commenters [2] for bringing the issue to our attention. The authors neither agree nor disagree to this retraction. [1] Cabanac G, Labbe C, Magazinov A, 2021, Tortured phrases: A dubious writing style emerging in science. Evidence of critical issues affecting established journals arXiv:2107.06751v1 [2] https://pubpeer.com/publications/4387C6F158C04F6E97898C3B5548CE Retraction published: 17 May 2023

The Role of Transforming Growth Factor-β1 Gene Polymorphism and Its Serum Levels in Hashimoto's Thyroiditis.

TGF-β1 gene (TGFB1) is one of the target genes involved in genetic predisposition to autoimmune diseases, particularly Hashimoto's thyroiditis (HT). In the present study, we attempted to investigate whether -509C/T SNP (rs1800469) in the promoter of TGFB1 is associated with the genetic susceptibility and clinical characteristics of Bulgarian patients with HT. We also analyzed serum TGF-β1 levels in different stages of the disease and its association with the -509C/T polymorphism in the TGFB1 promoter. The study recruited 121 female out-patients with autoimmune thyroiditis and 250 agematched healthy women (HC). Genotyping of the rs1800469 was performed by restriction fragment length polymorphism (RFLP)-PCR assay. The serum concentrations of latent acid-activated TGF-β1 protein were determined by the quantitative sandwich ELISA method. Upon testing different types of inheritance, a significant risk was found for heterozygotes (CT) with OR=1.640; p=0.05 under the codominant model. The significantly higher risk for developing Hypothyroidism was calculated again for CT-genotype patients with OR=1.789. According to the hormone reference values, a significant association of CT genotype with decreased TSH (75.4%) simultaneously with increased free T4 hormone (94%) levels was also calculated. When patients were stratified by genotype and compared to the same genotype in HC, we observed that the decreased levels in serum TGF-b1 were significant for patients who carried the C-allele in their genotype. We suggest that heterozygous genotype CT is a genetic risk factor for developing more severe HT due to enhanced free T4 serum level at the onset of the disease, before developing the hypothyroid stage.

Transforming growth factor-β1 gene polymorphisms with liver cirrhosis risk: A meta-analysis

Although several epidemiological studies have investigated the association of transforming growth factor-β1 (TGF-ß1) gene polymorphisms with the susceptibility to liver cirrhosis (LC), controversial results exist. Consequently, we performed a meta-analysis to accurately evaluate the relationship of TGF-ß1-509C/T and codon 10T/C polymorphisms with the risk of LC introduced by chronic hepatitis B/V virus (HBV/HCV) infection. A total of 9 case-control studies, involving 985 LC patients and 909 controls, were recruited for meta-analysis. The results suggested a significant association between the -509C/T polymorphism and LC risk in the total population. Stratification by ethnicity revealed similar associations in Egyptian and Caucasian populations, but not in Asian populations. Subgroup analyses by different etiologies also showed similar associations in HCV-induced LC, but not in HBV-induced LC. However, the overall data failed to show a significant association between codon 10T/C polymorphism and the risk of LC in the study. We concluded that TGF-ß1-509C/T polymorphism was significantly associated with LC susceptibility, while the codon 10T/C polymorphism seemed to have a limited role in predicting the occurrence of LC induced by HBV/HCV infection.

Transforming Growth Factor-β1 gene polymorphism and osteoporosis in postmenopausal egyptian women.

Transforming growth factor-β1 (TGF-β1) is a wide spread bone matrix protein that affect the function, formation and cell-cell interactions of osteoclasts and osteoblasts to regulate bone remodeling and sustain adequate bone mass. The aim of this study is to evaluate the role of the two polymorphism of transforming growth factor-β1 T869C and C-509T in developing osteoporosis in postmenopausal Egyptian women. This study was performed on 138 postmenopausal osteoporosis/osteopenic women and 128 postmenopausal female control group. There was a significant statistical difference in the CC, CT and TT (T869C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value &lt;0.001). There was a non-significant statistical difference in the CC, CT and TT (T-509C) genotype frequencies between the osteopenia/osteoporosis and control subjects (p value &lt;0.082). There was a significant statistical difference between TT,CT and CC of (T869C) and T score, Z score and calcium of osteopenia/osteoporosis group (p value &lt;0.001). There was a non-significant statistical difference between TT, CT and CC of (T-509C) and T score, Z score of osteopenia/osteoporosis group (p value 0.32,0.31),but there was a statistically significant difference between the three genotyping and serum calcium and creatinine (p value 0.04). Multivariate regression analysis showed that T869C polymorphism is a significant risk factor for osteopenia/ osteoporosis (OR 3.57, 95% CI= 1.56-5.67). We concluded that T869C polymorphism of the TGF-β1 gene has an impact on bone mineral density and enhancement of the susceptibility to osteopenia/osteoporosis in Egyptian women.

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.

Systematic review of cyclosporin A-induced gingival overgrowth and genetic predisposition.

This systematic review aimed to investigate the influence of gene polymorphisms on the development of gingival overgrowth in renal transplant patients treated with cyclosporin A. Electronic and hand literature searches were conducted by two independent reviewers in MEDLINE-Pubmed, Cochrane Library, ISI Web of Science, and SCOPUS Elsevier for prospective (case-control studies, cohort studies), cross-sectional, and retrospective studies published up to June 2016 (first week) in any language. Data were reviewed and extracted in duplicate independently. Methodologic quality assessment of the included studies was performed during the data extraction process. Due to the estimated high risk of bias and the heterogeneity of the included studies in regards to the variety of medications administered to study patients, a systematic review of the literature and not a meta-analysis of the data was performed. Fourteen articles meeting study inclusion criteria were selected for data extraction that examined the association between various genetic polymorphisms and gingival overgrowth in kidney transplant patients receiving cyclosporin A. Interleukin-1A, interleukin-10, transforming growth factor-β1 and androgen receptor gene polymorphisms may have a significant effect on an individual susceptibility to cyclosporin A-induced gingival overgrowth in renal transplant patients. Genetic polymorphisms seem to affect the development of cyclosporin A-induced gingival overgrowth in renal transplant patients. Pharmacogenetics and pharmacogenomics have the potential to determine the clinical outcome of a medication, the drug efficacy, and adverse drug reactions such as gingival overgrowth.

Transforming Growth Factor-β1 T869C Gene Polymorphism Is Associated with Acquired Sick Sinus Syndrome via Linking a Higher Serum Protein Level

BackgroundFamilial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-β1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-β1 is involved in the pathogenesis of acquired sick sinus syndrome.MethodsOverall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor-β1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-β1.ResultsTwo transforming growth factor-β1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16–3.75, P = 0.01). Consistently, the level of serum transforming growth factor-β1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3±3.4 ng/ml vs. 3.7±2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-β1 serum level than the TT genotype (4.25 ± 2.50 ng/ml vs. 2.71± 1.76 ng/ml, P = 0.028) in controls.ConclusionTransforming growth factor-β1 T869C polymorphism, correlated with high serum transforming growth factor-β1 levels, is associated with susceptibility to acquired sick sinus syndrome.

The Transforming Growth Factor-β1 (TGF-β1) Gene Polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and Susceptibility to Postmenopausal Osteoporosis

The aim of the present study was to integrate all the eligible studies and investigate whether the transforming growth factor-β1 (TGF-β1) gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) are correlated with postmenopausal osteoporosis (PMOP) risk.PMOP is a common skeletal disease and several genetic factors play an important role in the development and progression of PMOP. Significant associations between TGF-β1 gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and PMOP risk have been reported; however, some of these results are controversial.A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case–control studies investigating the relationship between TGF-β1 T869C and TGF-β1 T29C polymorphisms and the susceptibility of PMOP. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations.Eight studies involving 1851 cases and 2247 controls met the inclusion criteria after assessment by 2 reviewers. Overall, there were significant associations between TGF-β1 T869C and TGF-β1 T29C polymorphisms and PMOP (TGF-β1 T869C—C vs T: OR = 1.18, 95% CI = 1.02–1.36, P = 0.030; CC vs TT: OR = 1.38, 95% CI = 1.01–1.88, P = 0.042; CC vs CT/TT: OR = 1.39, 95% CI = 1.09–1.76, P = 0.008; TGF-β1 T29C—CT vs TT: OR = 1.25, 95% CI = 1.02–1.53, P = 0.032; CT/CC vs TT: OR = 1.37, 95% CI = 1.02–1.84, P = 0.035). In the subgroup analysis of ethnicity, significant association was observed between TGF-β1 T869C polymorphism and PMOP risk in Asian population (C vs T: OR = 1.18, 95% CI = 1.01–1.38, P = 0.043; CC vs TT: OR = 1.41, 95% CI = 1.01–1.97, P = 0.047; CT/CC vs TT: OR = 1.31, 95% CI = 1.03–1.66, P = 0.026; CC vs CT/TT: OR = 1.35, 95% CI = 1.03–1.75, P = 0.028); however, there was no significant association between TGF-β1 T869C polymorphism and PMOP risk in Caucasian population. With regard to TGF-β1 T29C polymorphism, significant association was also observed in Asian population (CT vs TT: OR = 1.37, 95% CI = 1.07–1.75, P = 0.013; CT/CC vs TT: OR = 1.54, 95% CI = 1.16–2.05, P = 0.003), while there was no significant association in Caucasian population.The TGF-β1 T869C and TGF-β1 T29C polymorphisms may be involved in susceptibility to PMOP, particular in Asian patients.

A single nucleotide polymorphism in the TGF-β1 gene (rs1982073 C>T) may contribute to increased risks of bone fracture, osteoporosis, and osteoarthritis: a meta-analysis.

Genetic factors have been shown to be of great importance for the pathogenesis of bone diseases, such as fracture, osteoporosis (OP), and osteoarthritis (OA). However, published studies on the correlations of transforming growth factor-β1 (TGF-β1) gene polymorphisms with bone diseases have been hampered by small sample sizes or inconclusive findings. We hence aimed at examining the relationships between a single nucleotide polymorphism in the TGF-β1 gene (rs1982073 C>T) with bone fracture, OP, and OA risks in this meta-analysis. A systematic electronic search of literature was conducted to identify all published studies in English or Chinese on the association between the TGF-β1 gene and fracture, OP, or OA risks. Data were abstracted independently by two reviewers. To investigate the strength of this relationship, crude odds ratios with 95% confidence intervals were used. An updated meta-analysis based on nine independent case-control studies were chosen (patients with fracture, OP, or OA = 1569; healthy controls = 1638). Results identified a higher frequency of rs1982073 C>T in patients with fracture, OP, or OA than in healthy controls. Ethnicity and genotyping method-stratified analysis under both models implied that the rs1982073 C>T polymorphism was positively correlated with the risk of fracture, OP, and OA among Asians under detection via the non-PCR-RFLP method. Disease-stratified results yielded that rs1982073 C>T may increase the risk of fracture, OP, and OA under the allele model, but was only significantly related to OP under the dominant model. According to the sample size-stratified analysis, subjects with the rs1982073 C>T polymorphism in the allele model were more likely to develop the three bone diseases in both the small and large sample size groups, and only in the large sample size under the dominant model. Our findings show that TGF-β1 rs1982073 C>T has a modest effect in increasing susceptibility to bone fracture, OP, and OA.

Interleukin 10 (IL10) and transforming growth factor β1 (TGFβ1) gene polymorphisms in persistent IgE-mediated cow's milk allergy

OBJECTIVES:The aim of this cross-sectional study was to evaluate whether interleukin 10 (IL10) and transforming growth factor β1 (TGFβ1) gene polymorphisms were associated with persistent IgE-mediated cow's milk allergy in 50 Brazilian children. The diagnostic criteria were anaphylaxis triggered by cow's milk or a positive double-blind, placebo-controlled food challenge. Tolerance was defined as the absence of a clinical response to a double-blind, placebo-controlled food challenge or cow's milk exposure.METHOD:The genomic DNA of the 50 patients and 224 healthy controls (HCs) was used to investigate five IL10 gene polymorphisms (-3575A/T, -2849A/G, -2763A/C, -1082G/A, -592C/A) and one TGFβ1 polymorphism (-509C/T).RESULTS:Among the five IL10 polymorphisms analyzed, homozygosis for the G allele at the -1082 position was significantly higher in the patients compared with the healthy controls (p = 0.027) and in the persistent cow's milk allergy group compared with the healthy controls (p = 0.001).CONCLUSIONS:Homozygosis for the G allele at the IL10 -1082G/A polymorphism is associated with the persistent form of cow's milk allergy.

Gene polymorphism of transforming growth factor-&amp;beta;1 in Egyptian patients with type 2 diabetes and diabetic nephropathy

Role of the transforming growth factor-β1 (TGF-β1) gene polymorphisms located at codons 10 and 25 in the genetic predisposition to type 2 diabetes (T2D) and in diabetic nephropathy (DN) in Egyptian patients was investigated. A case control study was done for 99 unrelated Egyptian patients with T2D (50 DN(-) and 49 DN(+)) and 98 age- and sex-matched healthy controls. TGF-β1 T869C (codon 10) and G915C (codon 25) polymorphism detection was done by amplification refractory mutation system method. DN(+) patients were younger, with higher body mass index, serum triglycerides, serum creatinine, and lower serum albumin than those in DN(-) patients. Moderate and bad grades of diabetic control were associated with DN (P < 0.001). The TGF-β1 (T869C) C allele, TC and TC + CC genotypes were significantly higher in patients; the T allele and TT genotype were significantly higher in controls (Pc < 0.001). The TGF-β1 TC genotype was associated with DN (Pc < 0.05). Non-significant differences were detected between T2D patients and controls in the frequencies of TGF-β1 (G915C) alleles and genotypes. In conclusion, these preliminary data showed that the TGF-β1 codon 10 C allele, and C allele-containing genotypes may be susceptible, and T allele/TT genotype may be protective factors for T2D and DN(+) complications.

Meta-analysis of the transforming growth factor-β1 polymorphisms and susceptibility to Alzheimer’s disease

The association between transforming growth factor-β1 (TGF-β1) gene polymorphisms and Alzheimer's disease (AD) risk has been widely reported, but results were somewhat controversial and underpowered. To derive a more precise estimation of the relationship between TGF-β1 polymorphisms and AD risk, we conducted a meta-analysis of all available case-control studies relating the T869C and/or C-509T polymorphisms of the TGF-β1 gene to the risk of developing AD. Eligible articles were identified by search of databases including Pub Med, Web of Science, the Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and the Wan Fang (Chinese) for the period up to March 2012. Finally, a total of 14 articles were identified, 10 with 1,657 cases and 6,971 controls for T869C polymorphism and 8 with 2,618 cases and 7,473 controls for C-509T polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model and recessive genetic model, respectively. Subgroup analysis was also performed by ethnicity. With respect to T869C and C-509T polymorphism, the combined results showed that there were no significant differences in genotype distribution between AD and control based on all studies. When stratifying for the race, there were also no statistically significant differences in genotype distribution between AD and controls. This meta-analysis did not provide an evidence of confirming association between the T869C and/or C-509T polymorphisms of the TGF-β1 gene and AD.

Association between transforming growth factor‐β1 polymorphisms and hepatocellular cancer risk: A meta‐analysis

The association between transforming growth factor-β1 (TGF-β1) gene polymorphisms and hepatocellular cancer (HCC) risk has been widely reported, but results were somewhat controversial. To derive a more precise estimation of the relationship between TGF-β1 polymorphisms and HCC risk, we conducted a meta-analysis of all available studies relating the C-509T and/or T869C polymorphisms of the TGF-β1 gene to the risk of developing HCC. Two investigators independently searched the MEDLINE, PubMed, Web of Science, Embase, CNKI (China National Knowledge Infrastructure) and CBM (Chinese Biomedical Literature database) for the period up to August 2011. A total of nine case-control articles were identified. Five studies with 1825 cases and 2869 controls for C-509T polymorphism, and six studies with 536 cases and 1496 controls for T869C polymorphism were included. In the overall analysis, no significant association between the polymorphisms and risk of HCC was observed. Stratified analysis showed that significant association between C-509T polymorphism and HCC was present only in controls with liver disease (T vs. C: odds ratio [OR] = 0.769, 95% confidence interval [CI] = 0.661-0.895; TT vs. CC: OR = 0.570, 95% CI = 0.412-0.788; TT/TC vs. CC: OR = 0.668, 95% CI = 0.523-0.854; TT vs. OR = 0.717, 95% CI = 0.550-0.934), but not in healthy controls. With respect to T869C polymorphism, only a decreased risk was found in recessive models in controls with liver disease. This meta-analysis supports that the TGF-β1 C-509T polymorphism may act in a protecting role in HCC susceptibility in populations with related liver disease.

Investigation of Transforming Growth Factor-β1 Gene Polymorphisms Among Iranian Patients With Chronic Hepatitis C

: Background: Chronic hepatitis C infection is caused by the hepatitis C virus (HCV), and its clinical complications include liver cirrhosis, liver failure, and hepatocellular carcinoma. Transforming growth factor-β1 (TGF-β1) is an important cytokine in cell growth and differentiation, angiogenesis, extracellular matrix formation, immune response regulation, and cancer development and progression.Objectives: The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in TGF-β1 and chronic HCV infection among patients referred to the Taleghani Hospital, Tehran, Iran between 2008 and 2010.Patients and Methods: In this case-control study, samples were collected using a convenience sampling method. We genotyped 164 HCV patients and 169 healthy controls for 3 SNPs in the TGF-β1 gene (-509 promoter, codon 10, and codon 25). We determined the SNP genotypes by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. To confirm the PCR-RFLP genotyping results, 10% of the samples were re-genotyped using a direct sequencing method.Results: There were no significant differences in the allelic frequency distribution of SNPs at -509 C/T, +869 C/T, or +915 G/C between HCV patients and the healthy controls. Genotyping results for all three polymorphic sites were similar with no statistically significant differences between the groups.Conclusions: Most of the Iranian patients (over 85%), both healthy controls and HCV patients, had the GG genotype at the +915 G/C position, resulting in a high level of TGF-β1 production. Therefore, we concluded that the SNPs investigated by us cannot be considered as prognostic factors for HCV infection in our population, despite being reported as prognostic markers in other populations. Moreover, there is a possibility that most of the population is susceptible to HCV infection. Implication for health policy/practice/research/medical education: Transforming growth factor beta-1 (TGF-β1) is a multifunctional cytokine that acts as a regulator of proliferation and cellular differentiation.Investigation of the association of single nucleotide polymorphisms (SNPs) in TGF-β1 gene sequence with increased or decreased individual’s susceptibility to chronic diseases such as hepatitis C infection could be helpful to find appropriate and population specific genetic biomarkers. Please cite this paper as: Romani S, Azimzadeh P, Mohebbi SR, Kazemian S, Almasi S, Naghoosi H, et al. Investigation of Transforming Growth Factor–β1 Gene Polymorphisms Among Iranian Patients With Chronic Hepatitis C. Hepat Mon. 2011;11(11):901-6. DOI: 10.5812/kowsar.1735143X.776

Investigation of Transforming Growth Factor-β1 Gene Polymorphisms Among Iranian Patients With Chronic Hepatitis C

Chronic hepatitis C infection is caused by the hepatitis C virus (HCV), and its clinical complications include liver cirrhosis, liver failure, and hepatocellular carcinoma.Transforming growth factor-β1 (TGF-β1) is an important cytokine in cell growthand differentiation, angiogenesis, extracellular matrix formation, immune responseregulation, and cancer development and progression. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in TGF-β1 and chronic HCV infection among patients referred to the Taleghani Hospital, Tehran, Iran between 2008 and 2010. In this case-control study, samples were collected using a convenience sampling method. We genotyped 164 HCV patients and 169 healthy controls for 3 SNPs in the TGF-β1 gene (-509 promoter, codon 10, and codon 25). We determined the SNP genotypes by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. To confirm the PCR-RFLP genotyping results, 10% of the samples were re-genotyped using a direct sequencing method. There were no significant differences in the allelic frequency distribution of SNPs at -509 C/T, +869 C/T, or +915 G/C between HCV patients and the healthy controls. Genotyping results for all three polymorphic sites were similar with no statistically significant differences between the groups. Most of the Iranian patients (over 85%), both healthy controls and HCV patients, had the GG genotype at the +915 G/C position, resulting in a high level of TGF-β1 production. Therefore, we concluded that the SNPs investigated by us cannot be considered as prognostic factors for HCV infection in our population, despite being reported as prognostic markers in other populations. Moreover, there is a possibility that most of the population is susceptible to HCV infection.