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Differential expression of SMAD3 transcripts is not regulated by cis-acting genetic elements but has a gender specificity

Genes & Immunity volume 10, pages 192–196 (2009)Cite this article

Abstract

As a key component of the transforming growth factor-β (TGF-β) pathway, SMAD3 plays an essential role in development and maintenance of self-tolerance. Furthermore, a recent study based on gene-expression profiling in donors of allogeneic hematopoietic cell grafts revealed that the level of expression of several components of the TGF-β pathway can predict the occurrence of graft-versus-host disease (GVHD) in recipients. The gene with the best GVHD predictive accuracy was SMAD3: no recipients suffered from GVHD when their donor cells expressed high levels of SMAD3 transcripts. The present study had two specific aims: to validate differential expression of SMAD3 transcripts in an independent and larger cohort of subjects and to determine whether interindividual differences were dictated by cis-acting genetic elements. In a cohort of 397 subjects, we found that SMAD3 transcript levels varied over a sixfold range. Analyses of SMAD3 single nucleotide polymorphisms and of SMAD3 promoter methylation patterns provide compelling evidence that interindividual differences in SMAD3 transcript levels do not result from in-cis genetic variations. Of note, part of the variance in SMAD3 expression was gender related as women expressed lower levels of SMAD3 transcripts than men.

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Acknowledgements

The study was supported by the Fonds de la Recherche en Santé du Québec (FRSQ) and the Leukemia and Lymphoma Society of Canada. CP holds a Canada Research Chair in Immunobiology. The Institute for Research in Immunology and Cancer is supported by the Canada Foundation for Innovation, the FRSQ and the Networks of Centres of Excellence through the Center of Excellence for Commercialization and Research program.

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Authors and Affiliations

  1. Department of Hematology, Hôpital Maisonneuve-Rosemont, Montréal, Quebec, Canada

    L Busque, C Belisle, S Provost & C Perreault

  2. Department of Medicine, Université de Montréal, Montréal, Quebec, Canada

    L Busque, C Belisle, S Provost, M Giroux & C Perreault

  3. Institute for Research in Immunology and Cancer, Montréal, Quebec, Canada

    M Giroux & C Perreault

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  1. L Busque
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  2. C Belisle
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  3. S Provost
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  4. M Giroux
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  5. C Perreault
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Correspondence to L Busque or C Perreault.

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Busque, L., Belisle, C., Provost, S. et al. Differential expression of SMAD3 transcripts is not regulated by cis-acting genetic elements but has a gender specificity. Genes Immun 10, 192–196 (2009). https://doi.org/10.1038/gene.2008.101

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