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

Genes Immun. 2009 Mar;10(2):192-6. doi: 10.1038/gene.2008.101. Epub 2009 Jan 8.


As a key component of the transforming growth factor-beta (TGF-beta) 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-beta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • DNA Methylation / genetics
  • Female
  • Gene Expression Regulation / physiology*
  • Graft vs Host Disease
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Living Donors*
  • Male
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic / genetics
  • Sex Characteristics*
  • Smad3 Protein / biosynthesis*
  • Smad3 Protein / genetics
  • Transforming Growth Factor beta / metabolism
  • Transplantation, Homologous


  • SMAD3 protein, human
  • Smad3 Protein
  • Transforming Growth Factor beta