title: Differential expression of SMAD3 transcripts is not regulated by cis-acting genetic elements but has a gender specificity.
abstract: 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.
authors.affiliation: Department of Hematology, Hôpital Maisonneuve-Rosemont, Montréal, Quebec, Canada. lbusque.hmr@ssss.gouv.qc.ca
authors.forename: L
authors.initials: L
authors.lastname: Busque
authors.forename: C
authors.initials: C
authors.lastname: Belisle
authors.forename: S
authors.initials: S
authors.lastname: Provost
authors.forename: M
authors.initials: M
authors.lastname: Giroux
authors.forename: C
authors.initials: C
authors.lastname: Perreault
mesh_terms: D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D019520:Living Donors; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012727:Sex Characteristics; D051900:Smad3 Protein / Q000096:biosynthesis* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta