TGFB1 mRNA expression and frequency of the + 869T>C and + 915G>C genetic variants: impact on risk for systemic sclerosis.

Systemic Sclerosis (SSc) is a chronic autoimmune disease characterized by immune disorder, microvascular damage, and fibrosis. TGFB1 gene encodes for the transforming growth factor isoform 1 (TGF-ß1), one of the most important pro-fibrotic cytokines. Therefore, variants in TGFB1 and changes in its expression could be associated with the pathogenesis of SSc. We aimed to evaluate the association of TGFB1 variants (+ 869T>C [rs1982073] and + 915G > C [rs1800471]) with the TGFB1 mRNA expression and SSc risk in the Southern Mexican population. We included 56 SSc patients and 112 control subjects (CS). The genetic variants were determined by the PCR-RFLP method. The TGFB1 mRNA expression was determined by qPCR. For the + 869T>C variant, the C allele was associated with SSc risk (OR = 1.733; CI = 1.087-2.762; p = 0.020). The C allele for the + 915G>C variant was also associated with SSc risk (OR = 11.168; CI = 1.289-96.754; p = 0.023). The relative expression of TGFB1 mRNA was 1.77-fold lower in SSc patients than in CS. Carriers of polymorphic alleles (TC or CC genotypes) for the + 869T>C variant showed 3.7-fold lower mRNA expression than the TT genotype in patients and 4.81-fold lower in CS. For the + 915G>C variant, patients with GA genotype had 1.78-fold lower mRNA expression than GG genotype carriers. In conclusion, the present study showed that + 869T>C and + 915G>C variants could be SSc risk factors for patients from Southern Mexico, and these genetic variants could induce lower mRNA expression of TGFB1.

Association of TGFB1 gene polymorphisms with cervical cancer in Bangladeshi women: A case-control study.

OBJECTIVES: Genetic susceptibility to cervical cancer in relation to transforming growth factor beta 1 (TGFB1) gene polymorphisms has not been investigated extensively among the women in Bangladesh. So, the aim of this study was to find out the correlation of the polymorphisms of TGFB1 C509T (rs1800469) and T869C (rs1800470) with the risk of cervical cancer among the Bangladeshi women. STUDY DESIGN: 134 cervical cancer patients and 102 age-sex matched healthy controls were included from two institutions in Bangladesh. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping two TGFB1 single nucleotide polymorphisms C509T (rs1800469) and T869C (rs1800470) in patients and controls. RESULTS: No significant correlation was found between polymorphisms C509T (rs1800469) and T869C (rs1800470) of TGFB1 gene with cervical cancer in Bangladeshi women. In case of the cervical cancer patients who had first degree relatives with cancer were prone to carry the polymorphic version of the TGFB1 gene polymorphism at C509T (OR = 5.597, 95% CI = 1.224-25.597, p < 0.05) but may not result in the increase of developing cervical cancer. CONCLUSION: In summary, two polymorphisms C509T and T869C of TGFB1 gene may not be associated with cervical cancer risk in Bangladeshi women.

A link between promoter polymorphisms of the transforming growth factor ß1 (TGFB1) and TGF-ß1 receptor II (TGFBR2) genes and relapsing-remitting multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is a chronic progressive autoimmune disease characterised by nerve demyelination, mediated by myelin-specific Th1 autoreactive cells. Transforming growth factor ï¢1 (TGF-1) is a regulatory cytokine involved in MS aetiology by maintaining CD4+ cell differentiation and preventing autoimmune responses. Because of the important role of the TGF-1 signalling pathway in MS aetiopathogenesis, we aimed to investigate the association of two DNA polymorphisms: TGFB1C[-509]T and TGFBR2G[-875]A and their combined genotypes with the risk of MS development in a cohort of Bulgarian patients. The effect of the two promoter polymorphisms on the disease onset was also assessed. MATERIAL AND METHODS: In the study, a cohort of 183 patients with relapsing-remitting multiple sclerosis (RRMS) and 307 sex- and age-matched healthy subjects were recruited. Genotyping of the TGFB1C[-509]T (rs1800469) and TGFBR2G[-875]A (rs3087465) polymorphisms was performed by PCR-RFLP and PIRA-PCR approaches. RESULTS: Frequencies of the TGFB1T[-509]T genotype and TGFB1[-509]*T-allele were lower in RRMS men than in control healthy men (15.7% vs. 26.9%, 37.3% vs. 50.7%, respectively). Among males, the TGFB1T[-509]T genotype was related to a significantly reduced risk of RRMS (OR = 0.360, 95% CI: 0.126-1.028, p = 0.05) in comparison to the TGFB1C[-509]C genotype. Also, TGFB1[-509]*T-allele was more common in men with RRMS than in healthy men relative to the TGFB1[-509]*C-allele and was associated with a statistically significant protective effect (OR = 0.576, 95% CI: 0.341-0.974, p = 0.039). The combination of TGFB1T[-509]T/TGFB1T[-509]C and TGFBR2G[-875]A genotypes among men was associated with a significant protective effect compared to the wild-type homozygous TGFB1C[-509]C and TGFBR2G[-875]G genotypes (OR = 0.268, 95% CI: 0.088-0.818, p = 0.018). No significant association between rs1800469 and rs3087465 was observed among females with and without (controls) RRMS. CONCLUSIONS: In summary, we suggest that in males, a higher TGF-1 level determined by TGFB1T[-509]T genotype in combination with the TGFBR2G[-875]A genotype might be a protective factor against RRMS development.

TGFB1 and LAMA1 gene polymorphisms in children with high myopia.

OBJECTIVE: To investigate TGFB1 and LAMA1 gene polymorphisms in children with high myopia in order to determine the genetic basis of large myopic shifts causing severe visual impairment and complications. METHODS: Seventy-four children with high myopia (≥6 diopters [D]; study group) and 77 emmetropic children (±0.5D; control group) were included. Genetic and polymorphism analyses were performed in the Medical Genetics Laboratory using DNA purified from the patients' blood samples. RESULTS: Mean ages of the patients were 7.1±3 (3-13) and 9.6±1.8 (6-13) years in the study and control groups, respectively. Mean refraction in the high myopia group were -10.1±4.3D in the right and -8.9±3.6D in the left eye. LAMA1 gene analysis of the study group revealed heterozygous mutations in 34 patients (45.9%), homozygous mutations in 25 patients (33.8%), and no mutations in the remaining 15 patients (20.3%). In the control group, there were 31 subjects (40.3%) with heterozygous, 27 (35.1%) with homozygous LAMA1 mutations, and no mutations in 19 (24.7%) (p=0.73). TGFB1 gene analysis showed heterozygous mutations in 32 (43.2%) and homozygous mutations in 10 patients (13.5%) in the study group, while 32 patients (43.2%) had no mutations. In the control group, 35 subjects (45.5%) had heterozygous, 8 (10.4%) had homozygous, and 34 (44.1%) had no TGFB1 mutations (p=0.36). CONCLUSION: This is the first study to simultaneously examine two genes in high myopia in a Turkish population. However, we observed no significant differences in TGFB1 and LAMA1 gene polymorphisms in patients with high myopia compared to healthy subjects.

Progressive diaphyseal dysplasia with right transverse sinus stenosis: a case report / 中华神经科杂志

Progressive diaphyseal dysplasia , also called Camurati-Engelmann disease (CED), is a kind of autosomal dominant disease mainly involved in long diaphysis , characterized as progressive and symmetric cortical thickening as well as low prevalence.The pathogenic gene of the disease is TGFB 1 located in 19q13, resulting in abnormal bone metabolism.We report a young woman suffering from CED , mainly presented as decreased visual acuity , chronic high intracranial pressure and skull damages by cerebral angiography.The digital subtraction angiography revealed the right transverse sinus stenosis .We first revealed a CED patient with chronic high intracranial pressure caused by sinus stenosis , and selected intravascular therapy for the sinus stenosis.

Association of TGFB1 -509C/T polymorphism gene with clinical variability in cystic fibrosis patients: A case-control study.

PURPOSE: In this work, we are interested to study the implication of -509C/T polymorphism, located in the promoter region of TGFB1 (transforming growth factor ß1), in the phenotypic variability of CF patients. PATIENTS AND METHODS: The present study enrolled 111 CF patients and 100 healthy control subjects. The study of the -509C/T polymorphism was performed using PCR-RFLP method. RESULTS: We found that patients carried non-F508del homozygous mutation with TT genotype was associated to lung symptoms (P=0.04). This association was not found in the sub-groups of patients with F508del at homozygous state P=0.145. No association was found between this polymorphism and the variability of digestive, pancreatic and ileus meconial symptoms. CONCLUSION: On the basis of our results, the -509C/T polymorphism of the TGFB1 gene seems to be a modulator factor of cystic fibrosis.

Skeletal Dysplasia Presenting as a Neuromuscular Disorder - Report of a Family with Camurati-Engelmann Syndrome.

We report the case of a 28-year-old female with progressive diaphyseal dysplasia, who presented with history of a similar neuromuscular condition. Clinical, radiological and molecular data confirmed Camurati-Engelmann Disease (CED). This is the first Romanian family who was diagnosed with CED.

Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase  1 (TIMP1) genes polymorphisms. For this purpose we used the transmission disequilibrium test (TDT). The group investigated was comprised of 100 nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents. It was found that HLA-DRB1*15alleleandMMP9*-1562C allele were transmitted from healthy heterozygous parents to affected children more frequently than alternative alleles (p  =  0.02 andp  =  0.04, respectively). Another family-based method, AFBAC (affected family-based control), showed MS association with HLA-DRB1*15, but not with theMMP9*-1562C allele.