For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
32
views
41
references
 Top references
cited by
10
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      302
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Association of tumor necrosis factor alpha gene polymorphism G-308A with pseudoexfoliative glaucoma in the Pakistani population

      research-article

      Read this article at

      ScienceOpenPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose

          The purpose of the present study was to determine the role of the tumor necrosis factor alpha ( TNF-α) gene polymorphism G-308A and total serum immunoglobulin E (TsIgE) levels in the onset of pseudoexfoliation glaucoma (PEXG) in Pakistani patients.

          Methods

          The TNF-α polymorphism G-308A was analyzed in 122 patients with PEXG and 126 healthy unrelated controls by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). TsIgE levels were determined by solid-phase enzyme-linked immunosorbent assay (ELISA).

          Results

          The AA and GA genotypes were strongly associated with PEXG (p<0.001), with an odds ratio (OR) of 0.07 (95% confidence interval [CI]=0.02-0.27) and 0.24 (95% CI=0.12-0.51), respectively, while the GG genotype was found at a higher frequency in controls as compared to patients (p<0.001) OR=8.95 (95% CI=4.55–17.81). No significant difference was found in TsIgE levels of both patients and controls (p=0.86).

          Conclusion

          The present study concludes that the TNF-α polymorphism G-308A is strongly associated with PEXG. To our knowledge this is the first study in southeast Asia which demonstrates a strong association of a TNF-α polymorphism with PEXG.

          Related collections

          Most cited references41

          • Record: found
          • Abstract: found
          • Article: not found

          Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation.

          A Wilson, J A Symons, T McDowell … (1997)
          Tumor necrosis factor alpha (TNF alpha) is a potent immunomodulator and proinflammatory cytokine that has been implicated in the pathogenesis of autoimmune and infectious diseases. For example, plasma levels of TNF alpha are positively correlated with severity and mortality in malaria and leishmaniasis. We have previously described a polymorphism at -308 in the TNF alpha promoter and shown that the rare allele, TNF2, lies on the extended haplotype HLA-A1-B8-DR3-DQ2, which is associated with autoimmunity and high TNF alpha production. Homozygosity for TNF2 carries a sevenfold increased risk of death from cerebral malaria. Here we demonstrate, with reporter genes under the control of the two allelic TNF promoters, that TNF2 is a much stronger transcriptional activator than the common allele (TNF1) in a human B cell line. Footprint analysis using DNase I and B cell nuclear extract showed the generation of a hypersensitive site at -308 and an adjacent area of protection. There was no difference in affinity of the DNA-binding protein(s) between the two alleles. These results show that this polymorphism has direct effects on TNF alpha gene regulation and may be responsible for the association of TNF2 with high TNF alpha phenotype and more severe disease in infections such as malaria and leishmaniasis.
          Article 0 comments Cited 228 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma.

            Toru Nakazawa, Chifuyu Nakazawa, Akihisa Matsubara … (2006)
            Glaucoma is a widespread ocular disease characterized by a progressive loss of retinal ganglion cells (RGCs). Previous studies suggest that the cytokine tumor necrosis factor-alpha (TNF-alpha) may contribute to the disease process, although its role in vivo and its mechanism of action are unclear. To investigate pathophysiological mechanisms in glaucoma, we induced ocular hypertension (OH) in mice by angle closure via laser irradiation. This treatment resulted in a rapid upregulation of TNF-alpha, followed sequentially by microglial activation, loss of optic nerve oligodendrocytes, and delayed loss of RGCs. Intravitreal TNF-alpha injections in normal mice mimicked these effects. Conversely, an anti-TNF-alpha-neutralizing antibody or deleting the genes encoding TNF-alpha or its receptor, TNFR2, blocked the deleterious effects of OH. Deleting the CD11b/CD18 gene prevented microglial activation and also blocked the pathophysiological effects of OH. Thus TNF-alpha provides an essential, although indirect, link between OH and RGC loss in vivo. Blocking TNF-alpha signaling or inflammation, therefore, may be helpful in treating glaucoma.
            Article 0 comments Cited 130 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Activated microglia in the human glaucomatous optic nerve head.

              Nicholas Neufeld, L. Yuan (2001)
              To investigate the distribution and potential participation of microglia, the resident defense cells of the central nervous system, in the optic nerve head (ONH) in glaucoma, histological paraffin sections of optic nerves from normal and glaucoma patients with mild to advanced nerve damage were studied using double labeling immunohistofluorescence. A monoclonal antibody for HLA-DR, indicating activated microglia, was colocalized with antibodies for functional proteins. In normal ONHs, microglia do not contain TGF-beta2, COX-2, or TNF-alpha and are not positive for PCNA; however, in glaucomatous ONHs, microglia contain abundant TGF-beta2, TNF-alpha, and PCNA. In glaucomatous eyes, a few microglia are usually positive for COX-2. In normal ONHs, there are rarely microglia containing TGF-beta1, NOS-2, TSP, TIMP-2, and CD68, but, in glaucomatous tissue, a few microglia are positive from the prelaminar to the postlaminar regions. MMP-1, MMP-2, MMP-3, and MMP-14 are constitutively present in the perivascular microglia in normal ONHs and appear to be more abundant in glaucomatous tissue. COX-1, TNF-R1, TIMP-1, and c-fms are constitutively present in normal tissues and appear to be increased in microglia in the glaucomatous ONHs. HSP27 is not present in microglia. In glaucomatous ONHs, microglia become activated and phagocytic and produce cytokines, mediators, and enzymes that can alter the extracellular matrix. Our findings suggest that activated microglia may participate in stabilizing the tissue early in the disease process, but, as the severity of the glaucomatous damage increases, the activities of microglia may have detrimental consequences for the pathological course of glaucomatous optic neuropathy. Copyright 2001 Wiley-Liss, Inc.
              Article 0 comments Cited 111 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Mol Vis
                Journal ID (publisher-id): MV
                Title: Molecular Vision
                Publisher: Molecular Vision
                ISSN (Electronic): 1090-0535
                Publication date Collection: 2009
                Publication date (Electronic): 22 December 2009
                Volume: 15
                Pages: 2861-2867
                Affiliations
                [1 ]Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan
                [2 ]Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
                [3 ]Shifa College of Medicine, Islamabad, Pakistan
                [4 ]Al-Shifa Trust Eye Hospital Rawalpindi, Pakistan
                [5 ]Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
                Author notes
                Correspondence to: Raheel Qamar, Dean Faculty of Sciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad-45600, Pakistan. Phone: +92-51-9235033; FAX: +92-51-4442805; email: raheelqamar@ 123456hotmail.com
                Article
                Publisher ID: 302 Publisher ID: 2009MOLVIS0416
                PMC ID: 2796874
                PubMed ID: 20029655
                SO-VID: 3eda1c41-a476-4e83-a20e-e3906d04a066
                Copyright © Copyright © 2008 Molecular Vision.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 30 November 2009
                Date accepted : 15 December 2009
                Categories
                Subject: Research Article
                Custom metadata
                GalleyStatus Export to XML
                corr-author Qamar

                ScienceOpen disciplines: Vision sciences
                Data availability:
                ScienceOpen disciplines: Vision sciences

                Comments

                Comment on this article

                Similar content302

                See all similar

                Cited by10

                See all cited by

                Most referenced authors570

                See all reference authors