Genetic susceptibility to dupuytren disease: association of Zf9 transcription factor gene.
Transforming growth factor beta 1 (TGF-beta 1) is a key fibrogenic cytokine that has been shown to stimulate fibroblast proliferation and extracellular matrix deposition and has been implicated in the pathogenesis of Dupuytren disease. Zf9 is a transcription factor that increases TGF-beta 1 expression in tissue. The authors previously demonstrated a lack of association between common TGF-beta 1 and TGF-beta 2 polymorphisms and Dupuytren disease. Therefore, Zf9 transcription factor represents an additional candidate susceptibility gene for investigating hereditary predisposition to Dupuytren disease. Dupuytren disease, or Dupuytren contracture, is a progressive and recurrent fibroproliferative disease of unknown etiology that affects the human hands. It is often a familial disorder affecting Northern European Caucasians. Genes implicated in the development of Dupuytren disease have not yet been found. Using a polymerase chain reaction-restriction fragment polymorphism method, the authors genotyped a novel single nucleotide polymorphism in the 3' untranslated region of the Zf9 gene. A case-control association study of 138 patients with Dupuytren disease versus 255 controls demonstrated a statistically significant difference in the genotype and allele frequencies between patients and controls for Zf9 gene polymorphism. Presence of the G allele versus the A allele is associated with an increased risk of developing Dupuytren disease (odds ratio, 1.9; 95 percent confidence interval, 1.2 to 2.9). The authors believe this to be the first report of a positive genetic association study in Dupuytren disease using single nucleotide polymorphisms.
Bayat
Ardeshir
A
Center for Integrated Genomic Research and Division of Cell Immunology and Development, School of Biological Sciences, University of Manchester, United Kingdom. ardeshir.bayat@man.ac.uk
Watson
J Stewart
JS
Stanley
John K
JK
Ferguson
Mark W J
MW
Ollier
William E R
WE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D015331:Cohort Studies; D004387:Dupuytren Contracture / Q000175:diagnosis / Q000235:genetics*; D004739:England; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins; D018570:Risk Assessment; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D044465:White People / Q000235:genetics
C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2