A link between promoter polymorphisms of the transforming growth factor β1 (TGFB1) and TGF-β1 receptor II (TGFBR2) genes and relapsing-remitting multiple sclerosis

Abstract

Introduction: Multiple sclerosis (MS) is a chronic progressive autoimmune disease characterised by nerve demyelination, mediated by myelin-specific Th1 autoreactive cells. Transforming growth factor β1 (TGF-β1) 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-β1 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 TGF-BR2G[-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, p = 0.05) in comparison to the TGF-B1C[-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 ]A genotypes among men was associated with a significant protective effect compared to the wild-type homozygous TGFB1C 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-β1 level determined by TGFB1T[-509]T genotype in combination with the TGFBR2G[-875]A genotype might be a protective factor against RRMS development.

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

“…No entanto, alguns estudos investigaram outras doenças. Grigorova et al (27) avaliaram a associação entre o polimorfismo rs1800469 do gene TGFB1 e o polimorfismo rs3087465 do gene TGFBR2 e episódios frequentes de atividade da doença em pacientes com esclerose múltipla. Os autores observaram maior concentração de TGFB1 determinada pelo genótipo TGFB1 em combinação com o genótipo TGFBR2 e concluíram que essa combinação atuou como fator protetor contra a esclerose múltipla remitente-recorrente.…”

“…Os autores observaram maior concentração de TGFB1 determinada pelo genótipo TGFB1 em combinação com o genótipo TGFBR2 e concluíram que essa combinação atuou como fator protetor contra a esclerose múltipla remitente-recorrente. (27) Jin et al (28) analisaram a associação entre os polimorfismos supracitados e o carcinoma de células escamosas do esôfago. Os autores concluíram que indivíduos portadores de genótipos variantes desses polimorfismos apresentavam risco significativamente reduzido de carcinoma de células escamosas do esôfago.…”

Genetic variation of TGF-ΒR2 as a protective genotype for the development of colorectal cancer in men

“…The risk of gastric cancer was notably lower among subjects who carried both the TGF-Β1 -509C and TGF-ΒR2 -875A allele genotypes. We also demonstrated that a combination of TGF-Β1T [-509] T with the TGF-ΒR2G [-875] A genotype might be a protective factor against relapsing-remitting multiple sclerosis development in men[ 15 ].…”

“…We performed the genotyping of the TGF-ΒR2 G [-875] A (rs3087465) by primer-introduced restriction analysis-polymerase chain reaction (PCR) assay[ 15 ]. The primer sequences were the following: forward primer- 5’-GCAAGAAAGGAAATTTGA AAGTTTGT-3’ and reverse primer 5’-TCACCTGAATGCTTGTGCTTTT-3’.…”