Association of polymorphisms of the transforming growth factor-β1 gene with the rate of progression of HCV-induced liver fibrosis

Gewaltig, Jan; Mangasser-Stephan, Kerstin; Gartung, Carsten; Biesterfeld, Stefan; Gressner, A. M.

doi:10.1016/s0009-8981(01)00738-0

Cited by 106 publications

(89 citation statements)

References 50 publications

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“…In contrast with previous results, [17][18][19][20][21]36 we did not find a significant difference in plasma levels of TGF-β1 depending on codon 10 genotype in either patients or donors. This lack of effect may be due to the fact that the subjects did not have a homogenous state of immune activation (donors were in a resting state and patients were under different conditions depending on the stage of disease, or recent chemotherapy).…”

Section: Ii-iv (%) Iii-iv (%)contrasting

confidence: 99%

“…Both polymorphisms are part of the signal sequence peptide 10,[14][15][16] and could, therefore, cause alterations in cytokine secretion. While codon 25 SNP have been consistently associated with decreased plasma levels, 17,18 conflicting data have been published regarding the impact of codon 10 SNP on plasma levels of TGF-β1. [17][18][19][20][21][22] These polymorphisms have been associated with an increased incidence of breast and colorectal neoplasia 20,23 and worse outcome following solid organ transplantation 24 and sibling HSCT.…”

Section: Introductionmentioning

confidence: 99%

“…While codon 25 SNP have been consistently associated with decreased plasma levels, 17,18 conflicting data have been published regarding the impact of codon 10 SNP on plasma levels of TGF-β1. [17][18][19][20][21][22] These polymorphisms have been associated with an increased incidence of breast and colorectal neoplasia 20,23 and worse outcome following solid organ transplantation 24 and sibling HSCT. 5,25,26 To date there is no published evidence on the possible role of these SNP in unrelated donor HSCT, or on plasma TGF-β1 levels and clinical outcomes following transplantation.…”

Section: Introductionmentioning

confidence: 99%

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Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

Berro¹,

Mayor²,

Maldonado-Torres³

et al. 2009

Haematologica

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BackgroundMany genetic factors play major roles in the outcome of hematopoietic stem cell transplants from unrelated donors. Transforming growth factor β1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes. Design and MethodsWe investigated the impact of single nucleotide polymorphisms at codons 10 and 25 of TGFB1, the gene encoding for transforming growth factor β1, on outcomes in 427 myeloablative-conditioned transplanted patients. In addition, transforming growth factor β1 plasma levels were measured in 263 patients and 327 donors. ResultsPatients homozygous for the single nucleotide polymorphism at codon 10 had increased non-relapse mortality (at 3 years: 46.8% versus 29.4%, P=0.014) and reduced overall survival (at 5 years 29.3% versus 42.2%, P=0.013); the differences remained statistically significant in multivariate analysis. Donor genotype alone had no impact, although multiple single nucleotide polymorphisms within the pair were significantly associated with higher non-relapse mortality (at 3 years: 44% versus 29%, P=0.021) and decreased overall survival (at 5 years: 33.8% versus 41.9%, P=0.033). In the 10/10 HLA matched transplants (n=280), recipients of non-wild type grafts tended to have a higher incidence of acute graft-versus-host disease grades II-IV (P=0.052). In multivariate analysis, when analyzed with patients' genotype, the incidences of both overall and grades II-IV acute graft-versushost disease were increased (P=0.025 and P=0.009, respectively) in non-wild-type pairs. ConclusionsWe conclude that increasing numbers of single nucleotide polymorphisms in codon 10 of TGFB1 in patients and donors are associated with a worse outcome following hematopoietic stem cell transplantation from unrelated donors.Key words: stem cell transplantation, TGF-β1, polymorphisms, survival, graft-versus-host disease.Citation: Berro M, Mayor NP, Maldonado-Torres H, Cooke L, Kusminsky G, Marsh SGE, Madrigal JA, and Shaw BE. Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation. Haematologica. 2010; 95:276-283. doi:10.3324/haematol.2009 This is an open-access paper.Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

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Section: Ii-iv (%) Iii-iv (%)contrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

Berro¹,

Mayor²,

Maldonado-Torres³

et al. 2009

Haematologica

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“…The soluble guanylate cyclase enzyme catalyzes the release of two phosphate groups from the guanosine triphosphate (GTP) molecule, resulting in the production of cyclic guanosine monophosphate (cGMP) [4]. The cGMP activates cGMPdependent protein kinase (PKG), which phosphorylates a number of cellular proteins and may promote relaxation due to decreased Ca 2+ influx, inhibition of release and / or increased Ca 2+ storage in the sarcoendoplasmic reticulum [5]. Therefore, cGMP plays a key role in the regulation of cardiovascular homeostasis, including smooth muscle relaxation, platelet inhibition, and vascular growth and differentiation [6].…”

Section: Introductionmentioning

confidence: 99%

In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation

Martinelli¹,

Rodrigues²,

Moraes³

et al. 2018

J Pharm Pharm Sci

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-Purpose. In endothelial cells, investigate if the soluble guanylate cyclase (sGC) activation or stimulation is able to potentiate the relaxation in vessels. Methods. Aortic and coronary rings with and without endothelium were placed in a myograph and cumulative concentration-effect curves for DETA-NO or ataciguat were performed. Nitric oxide (NO) were measured by fluorescence or by selective electrode in human umbilical endothelial cells (HUVECs) in response to some treatments, including ataciguat, 8-BrcGMP and A23187. Results. The presence of the endothelium potentiated the relaxation induced by DETA-NO in aortic and coronary rings. In addition, in aortic rings the endothelium potentiated the relaxation induced by ataciguat. In the presence of nitric oxide synthase (NOS) inhibitor, the endothelium effect was abolished to DETA-NO or ataciguat, in both vessels. Ataciguat, 8-Br-cGMP and A23187 were able to induce NO production in HUVECs cells. In the presence of NOS inhibitor, the NO production induced by ataciguat and 8-Br-cGMP was abolished. Conclusions. Our results suggest that in aortic and coronary rings the endothelium potentiates the relaxation induced by activation or stimulation of sGC through a mechanism dependent of NOS activation.

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“…TGF-β1 inflammation-related cytokine production, and TGF-β1 gene expression or dysfunction are associated with liver fibrosis and hepatocellular carcinoma, as is chronic HBV infection (Gewaltig et al, 2002;Kim et al, 2003;Wang, 2003). Gong et al (2008) reported on the relationship between TGF-β1 gene rs2241715 polymorphism and hepatocellular carcinoma, wherein they found that the rs2241715TT genotype frequencies in patients with liver cirrhosis and hepatocellular carcinoma were higher than those of a control group; however, to date there is no related report on rs2241715 gene polymorphism and familial clustering of hepatocellular carcinoma.…”

Section: Relationship Between Tgf-β1 Gene Polymorphisms and Familial mentioning

confidence: 99%

TGF-β1 polymorphisms and familial aggregation of liver cancer in Guangxi, China

Wan

Huang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The goal of present study was to investigate the relationship between polymorphisms of TGF-β1 and familial aggregation of liver cancer in Guangxi Zhuang, Han, and Yao populations. We conducted a population-based case-control family study of liver cancer in Guanxi, China. A total of 214 individuals from 37 case families were surveyed for polymorphisms in TGF-β1. We genotyped six functional TGF-β1 polymorphisms: rs1800469, rs2241715, rs2241716, rs11466345, rs8105161, and rs747857. Levels of TGF-β1, hepatitis B surface antigen, and anti-hepatitis C virus in all serum samples were detected using the enzyme-linked immunoassay method, and presence of hepatitis B virus (HBV) DNA was determined using polymerase chain reaction amplification. A standardized questionnaire was used to collect information from subjects, including alcohol consumption, smoking, eating, and water drinking habits. The results were compared with those from 214 control individuals. The results showed that the TGF-β1 genotypes rs1800469, rs2241715, rs2241715, and rs8105161 were more frequent in patients than in controls. The risk factors for familial aggregation of liver cancer in Guangxi were determined, from high to low, to be: drinking sugared beverages > alcohol consumption > HBV DNA-positive > rs1800469 TT homozygous genotype > rs2241715 TT homozygous genotype. The results suggested that TGF-β1 rs1800469 TT and rs2241715 TT homozygote genotypes represent the genetic factors underlying familial clustering of liver cancer in Guangxi, and that drinking water use, alcohol consumption, and testing positive for HBV DNA are the main environmental factors contributing to familial aggregation of liver cancer in Guangxi.

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Association of polymorphisms of the transforming growth factor-β1 gene with the rate of progression of HCV-induced liver fibrosis

Cited by 106 publications

References 50 publications

Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

Association of functional polymorphisms of the transforming growth factor B1 gene with survival and graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation

TGF-β1 polymorphisms and familial aggregation of liver cancer in Guangxi, China

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