Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Glutathione S-transferase genotypes in systemic sclerosis and their association with clinical manifestations in early disease

Genes & Immunity volume 2, pages 236–238 (2001)Cite this article

Abstract

The glutathione S-transferases (GSTs) are a family of enzymes involved in limiting oxidative damage to tissues. Null alleles for one or more of the GST enzymes, especially GSTM1, reportedly occur more frequently in patients with Sjögren’s syndrome and systemic lupus erythematosus who possess certain autoantibodies. Because systemic sclerosis (SSc) is a disease in which oxidative damage has been hypothesized to contribute both to immune dysfunction and tissue damage, we sought to determine if patients from a multi-ethnic cohort of SSc patients with early disease (⩽5 years) were more likely than ethnically-matched normal controls to have null alleles for GSTM1 (M1) and/or GSTT1 (T1), and if the null allele status correlated with any major disease features. The data show that while M1 and T1 null genotypes were not significantly increased in SSc compared to ethnically matched controls, their frequencies (especially T1 nulls) were significantly higher among SSc patients with hypertension and pulmonary involvement. This suggests that GST genotype may be a genetic factor that contributes to clinical disease expression in SSc.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Rosen A, Casciola-Rosen L, Wigley F Role of metal-catalyzed oxidation reactions in the early pathogenesis of scleroderma Curr Opin Rheumatol 1997 9 538–543

    Article  CAS  Google Scholar 

  2. Bell DA, Taylor JA, Paulson DF et al Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer J Natl Cancer Inst 1993 85 1159–1164

    Article  CAS  Google Scholar 

  3. Heagherty AHM, Fitzgerald D, Smith A et al Glutathione S-transferase GSTM1 phenotypes and protection against cutaneous malignancy Lancet 1994 343 266–268

    Article  Google Scholar 

  4. Chen CL, Liu Q, Pui CH et al Higher frequency of glutathione S-transferase deletions in black children with acute lymphoblastic leukemia Blood 1997 89 1701–1707

    CAS  PubMed  Google Scholar 

  5. Morinobu A, Kanagawa S, Koshiba M et al Association of the glutathione S-transferase M1 homozygous null genotype with susceptibility to Sjögren’s syndrome in Japanese individuals Arthritis Rheum 1999 42 2612–2615

    Article  CAS  Google Scholar 

  6. Ollier W, Davies E, Snowden N et al Association of homozygosity for glutathione S-transferase GSTM1 null alleles with the Ro+/La-autoantibody profile in patients with systemic lupus erythematosus Arthritis Rheum 1996 39 1763–1764

    Article  CAS  Google Scholar 

  7. Mattey DL, Hassell AB, Dawes PT et al Influence of polymorphism in the manganese superoxide dismutase locus on disease outcome in rheumatoid arthritis: evidence for interaction with glutathione S-transferase genes Arthritis Rheum 2000 43 859–864

    Article  CAS  Google Scholar 

  8. Pemble S, Schroeder KR, Spencer SR et al Human glutathione S-transferase Theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism Biochem J 1994 300 271–276

    Article  CAS  Google Scholar 

  9. Reveille JD, Fischbach M, McNearney T et al Systemic sclerosis in three U.S. ethnic groups: a comparison of clinical, sociodemographic, serologic, and immunogenetic determinants Semin Arthritis Rheum 2001 30 (in press)

    Article  Google Scholar 

  10. Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee Preliminary criteria for the classification of systemic sclerosis (scleroderma) Arthritis Rheum 1980 23 581–590

    Article  Google Scholar 

  11. Clements P, Lachenbruch P, Seibold JR et al Inter- and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis J Rheumatol 1995 22 1281–1285

    CAS  PubMed  Google Scholar 

  12. LeRoy EC, Black C, Fleischmajer R et al Scleroderma (systemic sclerosis): classification, subsets and pathogenesis J Rheumatol 1988 2 202–205

    Google Scholar 

  13. Arnett FC, Reveille JD, Goldstein R et al Autoantibodies to fibrillarin in systemic sclerosis (scleroderma): an immunogenetic, serologic, and clinical analysis Arthritis Rheum 1996 39 1151–1160

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center –, Houston, TX, USA

    MB Tew, JD Reveille, FC Arnett, AW Friedman & FK Tan

  2. Division of Clinical Epidemiology, University of Texas Health Science Center –, Houston, TX, USA

    C Ahn

  3. Division of Rheumatology, The University of Texas Medical Branch at Galveston, TX, USA

    T McNearney

  4. Division of Rheumatology, The University of Texas – San Antonio Health Science Center, TX, USA

    M Fischbach

Authors
  1. MB Tew
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. JD Reveille
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. FC Arnett
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. AW Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T McNearney
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Fischbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Ahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. FK Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to FK Tan.

Additional information

This work was supported by grants from NIAMS: Specialized Center for Research in Scleroderma award IP50AR44888, the RGK Foundation and LASR Fund (Dr Arnett), and NIH:NCRR 3M01 RR02558–12S1 (Dr Tan).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tew, M., Reveille, J., Arnett, F. et al. Glutathione S-transferase genotypes in systemic sclerosis and their association with clinical manifestations in early disease . Genes Immun 2, 236–238 (2001). https://doi.org/10.1038/sj.gene.6363756

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6363756

Keywords

This article is cited by

Search

Advanced search

Quick links