TGF-β1 Gene Polymorphisms Research Articles

Association of TGFB1 Gene Polymorphism with Congenital Heart Disease

Association of TGFB1 Gene Polymorphism with Congenital Heart Disease

Association of MLL3 and TGF-β signaling gene polymorphisms with the susceptibility and prognostic outcomes of Stanford type B aortic dissection

ObjectiveThis study aims to investigate the association of lysine methyltransferase 2 C (MLL3) and transforming growth factor β (TGF-β) signaling-related gene polymorphisms with the susceptibility of Stanford type B aortic dissection (AD) and its clinical prognostic outcomes. The methods involved investigating the MLL3 (rs10244604, rs6963460, rs1137721), TGFβ1 (rs1800469), TGFβ2 (rs900), TGFR1 (rs1626340) and TGFR2 (rs4522809) gene polymorphisms. Logistic regression was performed to investigate the association between 7 single nucleotide gene polymorphisms (SNPs) and Stanford type B aortic dissection. The GMDR software was used to analyze gene-gene and gene-environment interactions. The odds ratio (OR) with a 95% confidence interval (CI) was employed to evaluate the association of genes and Stanford type B AD risk.ResultsGenotypes and allele distributions in the case and control groups showed significant differences (P < 0.05). Logistic regression has shown that the Stanford Type B AD risk was highest in individuals with the rs1137721 CT genotype (OR = 4.33, 95% CI = 1.51–12.40). Additionally, WBC, drinking, hypertension, triglycerides (TG), and low-density lipoprotein (LDL-C) were independent risk factors for Stanford Type B AD. Logistic regression showed that the Stanford Type B AD risk was highest in individuals with the MLL3 (rs1137721)-TT + CT and TGFβ1 (rs4522809)-AA genotype (OR = 6.72, 95% CI = 1.56–29.84), and lowest in those with the MLL3 (rs1137721)-CC and TGFβ1 (rs4522809)-AA + GG genotype (OR = 4.38, 95% CI = 0.92–20.83). However, the 55-month median long-term follow-up did not show statistical significance.ConclusionCarriers of both TT + CT of MLL3 (rs1137721) and AA of TGFβ1 (rs4522809) polymorphisms may be closely related to the development of Stanford type B AD. MLL3 (rs1137721), WBC, and TG/TC were found to be associated with the morbidity of Stanford type B AD. MLL3 (KMT2C) is associated with the TGF-β signaling pathway protein. The risk of Stanford type B AD is related to the interactions of gene-gene and gene-environment.

TGF-β1 and TGFβR2 Gene Polymorphisms in Patients with Unstable Angina.

Acute coronary syndromes result from a sudden reduction in the lumen of a coronary artery as a result of atherosclerotic plaque rupture, its swelling or the formation of thrombotic lesions. Many mediators with inflammatory, prothrombotic and proatherogenic effects have been shown to be involved, including numerous cytokines, chemokines, adhesion molecules and growth factors. TGF-β1 is a pleiotropic cytokine found in various cells that regulates cell growth, differentiation and matrix production. The aim of our study was to assess the association between polymorphisms in the TGF-β1 gene (rs1800469, rs1800470) and polymorphisms in the TGFBR2 receptor gene (rs6785358, rs9838682) and the risk of unstable angina, as well as selected clinical parameters affecting the risk of ischemic heart disease. The study included 232 patients with unstable angina. The diagnosis of unstable angina was made by typical clinical presentation and confirmation of significant coronary artery lumen stenosis (&gt;70%) during coronary angiography. There were no statistically significant differences in the distribution of TGFBR2 rs6785358 and rs9838682 genotypes and haplotypes between patients with unstable angina and control subjects. We observed increased values of plasma total and LDL cholesterol levels, as well as triglycerides, in patients with the TGFBR2 rs9838682 AA genotype. In patients with the TGFBR2 rs6785358 AA genotype, we noted increased BMI values. There were no statistically significant associations between other studied polymorphisms and clinical parameters. Polymorphisms in the TGF-β1 gene (rs1800469, rs1800470) and polymorphisms in the TGFBR2 receptor gene (rs6785358, rs9838682) are not significant risk factors for unstable angina in our population. The TGFBR2 gene rs9838682 polymorphism may influence the lipid parameters in patients with coronary artery disease.

Relation of TGF-β1 gene with the prognosis of patients with Covid-19

This study aimed to investigate the role of the TGF-β1 gene in SARS-CoV-2 infection. A total of 178 individuals diagnosed with Covid-19 participated and, they were divided in two groups related to the outcome (discharge or death). Genotyping of rs1800468 and rs1800469 polymorphisms of TGF-β1 gene was performed in 178 samples, using the allelic discrimination technique and, gene expression analysis was performed in 93 samples by Real Time PCR. There was no association between the genotypic frequencies of TGF-β1 gene polymorphisms analyzed with the prognosis of patients with Covid-19. There was no significant difference between gene expression and the clinical data evaluated. A statistically significant difference was observed in the expression of the TGF-β1 gene between the CT and TT genotypes of the rs1800469 polymorphism, with lower gene expression in the presence of the TT genotype. Regarding the rs1800468 polymorphism, no statistically significant difference was observed in the expression of the TGF-β1 gene in relation to the analyzed genotypes. The present study concluded that the rs1800468 and rs1800469 polymorphisms of the TGF-β1 gene are not associated with the prognosis of patients with Covid-19 and which the TT genotype of the rs1800469 polymorphism reduces the expression of TGF-β1.

Genetic polymorphisms and their effects on the severity of silicosis in workers exposed to silica in Brazil.

Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by inhalation of silica particles. Genetic factors might play a role in the severity silicosis. We sought to evaluate the influence of polymorphisms in the ACE, FAS, FASLG, NOS2, IL1RN, FAM13A, TGFB1, and TNF genes on the severity of silicosis. Nine polymorphisms were genotyped by PCR in a sample of 143 patients with silicosis in the state of Rio de Janeiro, Brazil. Fifty-seven patients (40%) were classified as having simple silicosis and 86 (60%) were classified as having complicated silicosis. The TT genotype of rs1800469 in the TGFB1 gene showed a protective effect for complicated silicosis (OR = 0.35; 95% CI, 0.14-0.92; p = 0.028) when compared with the other two genotypes (CC+CT). The polymorphic T allele of rs763110 in the FASLG gene (OR = 0.56; 95% CI, 0.31-0.99; p = 0.047), as well as a dominant model for the T allele (TT+CT: OR = 0.37; 95% CI, 0.15-0.96; p = 0.037), also showed a protective effect. When patients with simple silicosis despite having been exposed to silica for a longer time (> 44,229 hours) were compared with patients with complicated silicosis despite having been exposed to silica for a shorter time, the T allele of rs763110 in the FASLG gene (OR = 0.20; 95% CI, 0.08-0.48; p < 0.0001), as well as dominant and recessive models (OR = 0.06; 95% CI, 0.00-0.49; p = 0.01 and OR = 0.22; 95% CI, 0.06-0.77; p = 0.014, respectively), showed a protective effect against the severity of silicosis. It appears that rs1800469 polymorphisms in the TGFB1 gene and rs763110 polymorphisms in the FASLG gene are involved in the severity of silicosis. Given the lack of studies relating genetic polymorphisms to the severity of silicosis, these results should be replicated in other populations.

Molecular characterization and frequency of transforming growth factor beta 1 gene polymorphism and its relation to bone complications in Egyptian patients with β-thalassemia

Objective The objective of this study was to determine the frequency of transforming growth factor beta 1 (TGFβ1) C-509T gene polymorphism and its relation to bone complications in patients with β-thalassemia major in Egypt. Background Osteoporosis is the most prevalent bone complication in patients with β-thalassemia major despite regular blood transfusions and iron chelation therapy. It is characterized by low bone mineral density (BMD) resulting in reduced bone strength and increased risk of fractures. Genetic factors play an important role in the determination of BMD. The TGFβ1 gene, which encodes TGFβ1, is a strong candidate for susceptibility to osteoporosis, and several studies have reported associations between BMD and different polymorphisms of TGFβ1, although these studies have yielded conflicting results. Study design and methods Single nucleotide polymorphism in the TGFβ1 gene promoter (C-509T) was investigated in 100 regularly treated Egyptian children with β-thalassemia major by PCR/RFLP genotyping. BMD was measured by dual-energy radiograph absorptiometry and expressed as Z score. Results The frequency of TGFβ1 gene polymorphism C-509T genotypes in all studied patients was 6% for homozygous CC, 85% for heterozygous CT, and 9% for homozygous TT. C allele frequency was 48.5%, whereas T allele frequency was 51.5%. BMD Z score was significantly higher in TT genotype compared with CC genotype, with P value less than 0.05. Patients were grouped on the basis of BMD Z score: 51 (51%) patients with BMD deficit (Z score &lt;−1) and 49 (49%) with normal BMD (Z score ≥−1). TGFβ1 gene polymorphism C-509T genotypes were distributed differently between the two groups; the TT genotype frequency was lower in patients with BMD deficit (P&lt;0.05). Conclusion TGFB1 gene polymorphism C-509T is associated with BMD and genetic susceptibility to osteoporosis and may play a role in the pathogenesis and modification of bone complication in β-thalassemia major. BMD deficit is common in Egyptian children with β-thalassemia major. Analysis of this polymorphism at an early age could help in identification of thalassemic children at risk of osteoporosis and early management. However, large-scale studies are required to confirm these findings.

Lack of Association between IFN-γ, CXCL10 and TGF-β1 Gene Polymorphisms and Liver Complication in HIV-infected Thais.

Objective:Chronic liver disease has become a leading cause of illness and death in people living with HIV and the production of the cytokines IFN-γ and TGF-β1, and chemokine CXCL10 during chronic inflammation contributes to liver disease progression in HIV patients under long-term anti-retroviral therapy. This study aimed to examine association of IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T single nucleotide polymorphisms (SNPs) with liver complications in the HIV-infected Thais. Methods:A cross-sectional study was conducted in 200 Thai HIV patients who were evaluated for transaminitis and significant liver fibrosis by fibrosis-4 score (FIB-4), and genotypes for IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T SNPs using PCR-based methods. Result:There were high rates of transaminitis (30.1%) and significant liver fibrosis assessed by FIB-4 score > 1.45 (18.8%) in this group of patients, mostly under anti-retroviral therapy (73.0%). The genotypes and alleles of IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β1 -509C/T SNPs were not associated with either transaminitis or FIB-4 score > 1.45 (p > 005). Logistic regression analysis identified age and gender as risk factors, and CD4+ cell count higher than 350 cells/ul as a protective factor of liver fibrosis in this study group.Conclusion:The IFN-γ +874T/A, CXCL10 G-201A and C-1596T, and TGF-β11 -509C/T SNPs were not significantly associated with liver complication in HIV-infected Thais, mostly under ART.

Association between transforming growth factor-beta 1 polymorphisms and risk of pre-eclampsia: a meta-analysis

Purpose Pre-eclampsia (PE) is a common pregnancy-specific disorder characterized by hypertension and proteinuria. Previous studies have generated conflicting results regarding the association of transforming growth factor-beta 1 (TGF-β1) gene polymorphisms (+869 T/C, −509 C/T, +915 G/C, and −800 G/A) with PE risk. Therefore, we conducted this meta-analysis to more precisely assess the role of TGF-β1 gene polymorphisms in PE. Methods Eligible studies were retrieved from PubMed, Embase, Web of Science, Elsevier Science Direct, and several Chinese databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to calculate the associations. Results A total of 11 eligible studies (1463 cases/1754 controls) were included in this meta-analysis. A statistically significant association was found between the TGF-β1 + 869 T/C polymorphism and PE risk in the Asian population and in subgroup analyses of the Hardy-Weinberg equilibrium (HWE) in controls and healthy pregnant controls. There was a statistically significant association between TGF-β1 − 509 C/T polymorphism and PE risk among Asian women, and in the subgroup analysis of healthy pregnant controls. No obvious association was observed under any genetic model for the TGF-β1 + 915 G/C and −800 G/A polymorphisms and PE risk, or between the TGF-β1 + 869 T/C and −509 C/T polymorphisms and severity of PE. Conclusions The present study suggested that the TGF-β1 + 869 T/C and −509 C/T polymorphisms are associated with an increased risk of PE in the Asian population. Further case-controlled studies with larger sample sizes are needed to confirm our results.

IL-10 and TGF-β1 gene polymorphisms in Greek patients with recurrent aphthous stomatitis.

Background Recurrent aphthous stomatitis (RAS) is one of the most frequent inflammatory disorders of the oral mucosa. Cytokines, which play an important role in RAS pathogenesis, participate directly or indirectly in normal, immunological and inflammatory processes and are secreted from cells belonging to innate and adaptive immunity as a consequence of microbial and antigenic stimuli. Gene polymorphisms in specific cytokines may predispose to RAS development. The aim of this study was the investigation and association of IL-10 and TGF-β1 gene polymorphisms with RAS.Material and Methods Study’s cohort consisted of 60 Greek patients diagnosed with RAS, including 40 patients with minor, 10 patients with major and 10 with herpetiform aphthous ulcers. Forty age- and sex-matched control subjects were included in this study. DNA was extracted from whole blood samples of all patients and sequence-specific primers (SSP)-based polymerase chain reaction (PCR) was used for genotyping. Gene polymorphisms for cytokines IL-10 at loci -592 and -819 and for TGF-β1 at codon 10 were detected.Results Significant differences between patients with minor RAS and healthy controls were recorded for IL-10 genotypes distribution at position -592 (p=0.042) and -819 (p=0.045) with predominance of C/A and C/T genotypes in RAS patients, respectively. Also, in patients with minor and herpetiform aphthous ulcerations, heterozygous TGF-β1 genotype C/T at codon 10 was associated with increased risk of RAS (p=0.044 and p=0.020, respectively).Conclusions These data provide evidence that genetic predisposition for RAS and possibly its specific clinical variants is related with the presence of gene polymorphisms for specific cytokines, including IL-10 and TGF-β1, which, in turn, may vary according to geographic origin and genetic background. Key words:Recurrent aphthous stomatitis, aphthae, IL-10, TGF-β, gene polymorphisms, oral mucosa.

Подходы к молекулярно-генетической диагностике глазных проявлений пролиферативного синдрома для патофизиологически направленного лечения

Background: uncontrolled cell proliferation of the ocular blood network is one of the leading causes of blindness and low vision worldwide. We summarize relevant published data and our 5-year experience in searching treatment tools for excessive non-productive proliferation. Aim: to describe genetic patterns in patients with ocular blood network proliferation for predicting disease course and selecting adequate treatment. Patients and Methods: 1210 patients with proliferative ocular disorders, retinopathy of prematurity, and diabetes were enrolled. Patients were divided into three groups: (1) monogenic disorders, (2) proliferative vitreoretinopathy and diabetes mellitus, (3) retinopathy of prematurity. Follow-up was 6 to 36 months. Laboratory, genetic, and relevant clinical tests were pursued in all patients. Results: proprietary approach of bioinformatic analysis of whole exome/whole genome sequencing data allows for specifying the proliferative process’s prognosis and severity given clinical and genetic findings. This approach includes the analysis of gene mutations directly or indirectly involved in angiogenesis and key signaling pathways. The analysis of mutation identified in group 2 revealed 509C&gt;T TGFB1 gene polymorphism in two patients and c.3174G&gt;A IGF1R gene polymorphism in three patients. In group 3, the most common VEGFA gene polymorphisms were +13553C&gt;T, -634G&gt;C, +405G&gt;C (rs2010963), and -460C&gt;T (rs833061). Conclusion: specifying the prognosis of the course and severity of proliferative ocular disorders pathogenically-oriented targeted treatment requires specialized genetic testing using an improved data analysis approach. Keywords: proliferative syndrome, diabetes, retinopathy of prematurity, VEGFA, TGFB1, IGF1R, Stickler syndrome, Wagner syndrome, Wolframe syndrome, Marshall syndrome, Norrie disease, Coats disease, retinoschisis. For citation: Weener M.E., Bakunina N.A., Salmasi J.M. et al. Genetic testing of ocular manifestations of proliferative syndrome to provide pathophysiology-oriented treatment. Russian Journal of Clinical Ophthalmology. 2022;22(1):16–22 (in Russ.). DOI: 10.32364/2311-7729- 2022-22-1-16-22.

Glutathione S-Transferase Omega-2 and Transforming Growth Factor-β1 Polymorphisms in Iranian Glaucoma Patients.

Background To investigate the association of glutathione s-transferase omega 2 (GSTO2) (142N > D) and transforming growth factor-β1 (TGF-β1) (869T > C) gene polymorphisms on the pathogenesis of two common types of glaucoma (including primary open-angle glaucoma (POAG) and chronic angle-closure glaucoma (CACG)) in the Iranian population. Methods A total of 100 glaucoma patients (60% males and 40% females with an age mean ± SD of 34.66 ± 14.25 years; 56 cases of POAG and 44 cases of CACG) were enrolled in this study. GSTO2 (142N > D) and TGF-β1 (869T > C) polymorphisms were evaluated by PCR-based methods in patients and controls. Results At locus GSTO2 (142N > D), the odds of ND genotype with respect to DD and NN genotypes were 1.55 and 2.08 times higher in POAG and CACG patients compared to those of patients in the control group (95% CI1: 0.80–2.98; 95% CI2: 1.00–4.33) which was statistically significant in CACG patients. However, the odds of DD and NN genotypes against the reference genotype in two patients group were not statistically significant as compared to those of patients in the control group. There was a significant association between the ND genotype and male patients (OR = 2.28, 95% CI: 1.06–4.92). The analysis of TGF-β1 (869T > C) polymorphisms showed no significant difference between the genotypes of TGF-β1 (869T > C) polymorphisms in patients and control groups; however, the CT genotype of TGF-β1 significantly differed between female controls and patients (OR = 0.42, 95% CI: 0.18–0.96). Conclusion The presented results revealed that there was a significant association between the ND genotype of GSTO2 and the pathogenesis of glaucoma. Furthermore, this genotype can be considered as a sex-dependent genetic risk factor for the development of glaucoma. In contrast, the CT genotype of TGF-β1 is suggested to be a protective genetic factor against the pathogenesis of glaucoma.

The role of TGF-β1 gene polymorphisms in the development of post-transplant complications

Transforming growth factor beta 1 (TGF-β1) is an immunosuppressive and profibrogenic cytokine capable of influencing the development of graft rejection and graft fibrosis in solid organ recipients. The TGF-β gene has a significant polymorphism that may cause individual protein expression levels and be associated with post-organ transplant complications. It is believed that three TGFB1 polymorphic variants (rs1800469, rs1800470 and rs1800471) may be associated with the development of graft rejection, graft fibrosis and chronic dysfunction of a heart, liver or kidney transplant. A review of current literature presents the results of studies on the relationship between TGF-β1 gene polymorphisms and post-transplant complications in solid organ recipients. The findings of various studies of TGF-β1 gene polymorphism in solid organ recipients are not always unambiguous, and their results are often difficult to generalize even with the help of meta-analysis. Samples included in studies vary in terms of ethnicity, gender, age, and underlying medical conditions, while results are highly dependent on sample structure or latent relatedness. Currently available data suggest that TGFB1 polymorphism may determine a predisposition to the development of graft rejection, graft fibrosis and graft dysfunction in solid organ recipients, but this is not conclusive and requires further, larger studies.

Correlation analysis of TGF-β1 gene polymorphism and expression with incidence and severity of lumbar disc herniation.

Correlation analysis of TGF-β1 gene polymorphism and expression with incidence and severity of lumbar disc herniation.

Analysis of Associative Relationship of Allelic and Genotypical Variants of Polymorphism Rs 2010963 of the VEGFA Gene with Formation and Development of Ronchopathy

It is interesting to note that the adverse effect of this genotype was observed exclusively in patients with ronchopathy, while in patients with ronchopathy, the frequency of this genotype did not differ in comparison with the control group, i.e. there is a significant tendency to an increase in the genotype with an increase in the severity of the pathology. Material and methods. To solve the set tasks, 208 patients with various diseases of the upper respiratory tract, with nasal breathing disorders, causing ronchopathy, who were hospitalized in the ENT department of the multidisciplinary clinic of the Tashkent Medical Academy for 2015 to 2021, were examined. The control group consisted of 50 apparently healthy people who agreed to participate in the study (students, masters, clinical residents). Among the sick men there were 144 (73%), women – 64 (27%). The age of the patients ranged from 18 to 70 years, averaging 44.5 ± 6.8 years. Molecular genetic studies were carried out in the Department of Molecular Medicine and Cell Technologies of the RSNPMC Hematology. This part of the work consisted of several stages: 1. Blood sampling. 2. Isolation of DNA from peripheral blood lymphocytes. 3. Carrying out PCR. 4. Conducting electrophoresis and visualizing the results (if necessary). The analysis of the TGFb1 gene polymorphism associations was carried out using a case-control model (case-control, comparison of two samples). The sample “case” was formed from 104 patients with ronchopathy. Conclusion. Since this work is one of the few works on the study of the relationship between rs 2010963 of the VEGFA gene and the risk of developing ronchopathy, our data may become the subject of further discussions.

Analysis of Associative Relationship of Allelic and Genotypical Variants of Polymorphism Rs 2010963 of the VEGFA Gene with Formation and Development of Ronchopathy

It is interesting to note that the adverse effect of this genotype was observed exclusively in patients with ronchopathy, while in patients with ronchopathy, the frequency of this genotype did not differ in comparison with the control group, i.e. there is a significant tendency to an increase in the genotype with an increase in the severity of the pathology. Material and methods. To solve the set tasks, 208 patients with various diseases of the upper respiratory tract, with nasal breathing disorders, causing ronchopathy, who were hospitalized in the ENT department of the multidisciplinary clinic of the Tashkent Medical Academy for 2015 to 2021, were examined. The control group consisted of 50 apparently healthy people who agreed to participate in the study (students, masters, clinical residents). Among the sick men there were 144 (73%), women - 64 (27%). The age of the patients ranged from 18 to 70 years, averaging 44.5 ± 6.8 years. Molecular genetic studies were carried out in the Department of Molecular Medicine and Cell Technologies of the RSNPMC Hematology. This part of the work consisted of several stages: 1. Blood sampling. 2. Isolation of DNA from peripheral blood lymphocytes. 3. Carrying out PCR. 4. Conducting electrophoresis and visualizing the results (if necessary). The analysis of the TGFb1 gene polymorphism associations was carried out using a case-control model (casecontrol, comparison of two samples). The sample "case" was formed from 104 patients with ronchopathy. Conclusion. Since this work is one of the few works on the study of the relationship between rs 2010963 of the VEGFA gene and the risk of developing ronchopathy, our data may become the subject of further discussions.

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&gt;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 TGF-β1 and IL-10 Gene Polymorphisms with Osteoporosis in a Study of Taiwanese Osteoporotic Patients

Osteoporosis is a rising health threat in the increasingly aging world population. It is a common skeletal disease strongly linked to genetic predisposition. We aim to identify the effects of the anti-inflammatory TGF-β1- and IL-10-specific single-nucleotide polymorphism (SNP) combination on the risk for osteoporosis. We investigated and analyzed the relationships between three TGF-β1 SNPs (−509C/T, +869 T/C and +29T/C), one IL-10 SNP (+1927A/C) and the level of bone mineral density (BMD), as well as the risk of osteoporosis in Taiwanese osteoporotic patients. A total of 217 subjects were recruited, including 88 osteoporotic patients and 129 healthy controls, for SNPs, BMD and clinical characteristics statistical analyses. Females with TGF-β1 SNP (−509 C/C) and IL-10 SNP (+1927 C/C) genotypes showed a great benefit for femoral neck T-scores. However, the combination of TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/A) genotypes in all subjects showed a significant decrease in total hip BMD T-scores. The TGF-β1 SNP (−509 C/T) genotype in all subjects and TGF-β1 SNP (−509 T/T) and IL-10 SNP (+1927 A/C) genotypes in males showed positive effects on body height. The combination of the many SNPs in the anti-inflammatory TGF-β1 and IL-10 genes may be cooperatively involved in the development of osteoporosis. Our data suggested that the specific SNP combination of TGF-β1 (−509) and IL-10 (+1927) may act as a predictive factor for postmenopausal osteoporosis in Taiwanese women.

The association of transforming growth factor beta 1 gene polymorphisms with arthritis: a systematic review and meta-analysis.

The objective of this study was to explore the association between transformation growth factor beta 1 (TGF-β1) gene polymorphisms and different types of arthritis. PubMed, Medline, Web of Science, Cochrane Library, Biosis and four Chinese databases: China Biology Medicine, China National Knowledge Infrastructure, Wanfang and CQVIP, were searched. Studies that analyzed the association of the TGF-β1 polymorphisms with different types of arthritis were included. OR, 95% confidence interval and P value were calculated in three models including allele, dominant and recessive models, using D + L method. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. TGF-β1 869T > C polymorphism was significantly associated with rheumatoid arthritis (RA) in allele and recessive models, but not in dominant model (allele model T vs. C: OR = 1.30, 95% CI = 1.13-1.49, P < 0.001; recessive model CC vs. TT + TC: OR = 0.57, 95% CI = 0.43-0.76, P < 0.001; dominant model TT vs. TC + CC: OR = 1.20, 95% CI = 0.99-1.45, P = 0.063). Additionally, allele and recessive models showed that TGF-β1 -509C > T was significantly correlated with RA susceptibility, while dominant model revealed nonsignificant correlation (allele model: C vs. T: OR = 1.51; 95% CI = 1.00-2.28; P = 0.049; recessive model: TT vs. CC + TC: OR = 0.52, 95% CI = 0.37-0.72, P = 0.000; dominant model: CC vs. TT + TC: OR = 1.48; 95% CI = 0.79-2.76; P = 0.223). However, no significant association was found between TGF-β1 polymorphisms and ankylosing spondylitis (AS) or osteoarthritis (OA) risk. This study demonstrated that 869T > C, -509 C > T polymorphisms of TGF-β1 gene were associated with increased susceptibility of RA, while polymorphisms of TGF-β1 gene were not associated with OA and AS. These findings suggest that studying TGF-β1 genotype may be useful in the prevention and management of RA. However, more studies are needed to evaluate the association of TGF-β1 gene polymorphisms with the susceptibility of OA and AS.

The rs1800470 Polymorphism of the TGFB1 Gene Is Associated with Myocardial Fibrosis in Heart Transplant Recipients.

The transforming growth factor β1 (TGFβ1), whose level may depend on the polymorphism of the TGFB1 gene, is involved in the formation of myocardial fibrosis. Myocardial fibrosis in a cardiac allograft may lead to a heart’s structural and functional remodeling and subsequent dysfunction. The frequency of occurrence of alleles and genotypes of the TGFB1 gene polymorphic regions rs1800469, rs1800470, and rs1800471 in heart transplant recipients and their association with graft myocardial fibrosis were analyzed. Carriers of the CC genotype (p = 0.023, OR = 0.12, 95% CI: 0.017–1.0), and more often the G allele of rs1800471 (p = 0.023, OR = 7.76, 95% CI: 1.0–60.20), were found among heart transplant recipients less frequently than among healthy individuals. In patients with ischemic heart disease (IHD), the GG genotype was less common (p = 0.035, OR = 2.68, 95% CI: 1.061–6.793), while the A allele of rs1800469 was found more frequently (p = 0.035, OR = 0.37 95% CI: 0.148–0.942) than in patients with dilated cardiomyopathy (DCM). In heart transplant recipients with the AA genotype of rs1800470, myocardial fibrosis, verified by endomyocardial biopsy, was detected more often than in carriers of the G allele (OR = 10.4, 95% CI: 1.152–94.538, p = 0.013). The revealed differences suggest a relationship between TGFB1 gene polymorphism and graft myocardial fibrosis. Studies on a larger group of patients would make it possible to characterize the influence of genetic factors on the formation of myocardial fibrosis in heart transplant recipients.

TGF-β1 Gene Polymorphism and Its Correlation with Serum Level of TGF-β1 in Psoriasis Vulgaris Among Iraqi People.

PurposeMany cytokines have been implicated in the pathogenesis of psoriasis, among these the transforming growth factor-beta 1 (TGF-β1) can be endorsed by different mechanisms besides inhibiting keratinocytes proliferation. The role of genetic polymorphisms of TGF-β1 has been studied in various inflammatory diseases. Our aim is to study the correlation of TGF-β1 gene polymorphism at codon 10 and 25 with the expression of serum level of TGF-β1 in a sample of Iraqi psoriatic patients compared to the control group.Materials and MethodsA cross-sectional study involved 100 patients with psoriasis vulgaris and 50 sex- and age-matched healthy volunteers as control group. Serum and genomic DNA were prepared from peripheral blood samples. Amplification refractory mutation system–polymerase chain reaction technique (ARMS-PCR) had been applied for genotyping TGF-β1 codon 10 [rs1982073] and codon 25 [rs1800471] genetic polymorphisms. Enzyme-linked immunosorbent assay technique (ELISA) based on the sandwich principle was used for quantification of serum TGF-β1 level. Psoriasis Area and Severity Index (PASI) scoring was applied for determining the severity in psoriatic patients and classified accordingly to mild (PASI<7), moderate (PASI 7–12), severe (PASI>12) groups.ResultsStatistically significant difference was found in TGF-β1 gene polymorphism between psoriatic patients and control group at codon 10 (T869C) polymorphism (p=0.021) and codon 25 (G915C) polymorphism (p=0.040). No significant association was detected with the mean serum TGF-β1 level, severity of the disease, disease onset, gender, history of psoriatic arthritis, and smoking in both codons. Significant lower mean serum TGF-β1 level was found among psoriatic group (192.17 ± 531.12 ng/L) compared with controls (565.89 ± 1372.30 ng/L) (p = 0.018). Relation of mean serum TGF-β1 level with the onset of the disease was statistically significant (p = 0.004), early-onset disease group was lower (105.92 ± 68.02 ng/L) compared with the late-onset disease group (450.92 ±1027.79 ng/L). The mean serum TGF-β1 level showed no significant differences with the severity of psoriasis, gender, history of psoriatic arthritis, and smoking.ConclusionIraqi population showed a significant association between TGF-β1 gene polymorphism at codon 10 and 25 were with psoriasis susceptibility, and a significantly lower mean serum TGF-β1 level was detected in psoriatic patients.