title: The influence of transforming growth factor-beta1 gene polymorphisms on the severity of gingival overgrowth associated with concomitant use of cyclosporin A and a calcium channel blocker.
abstract: BACKGROUND
  The purpose of this study was to determine whether the prevalence and severity of gingival overgrowth in renal transplant recipients concomitantly treated with cyclosporin and a calcium channel blocker was associated with functional polymorphisms within the signal sequence of the transforming growth factor-(TGF)beta1 gene.
  
  
  METHODS
  The extent and severity of gingival overgrowth for 164 renal transplant recipients immunosuppressed with cyclosporin A and concomitantly taking a calcium channel blocker since transplant were entered into the study (86 in Manchester, 78 in Belfast). Two biallelic polymorphisms of the TGF-beta1 gene were studied at position +869, codon 10 (leucine to proline substitution), and position +915, codon 25 (arginine to proline substitution).
  
  
  RESULTS
  Subjects who were homozygous for proline at codon 10 had significantly higher overgrowth scores than those who were heterozygous (P= 0.03) or homozygous for leucine (P= 0.01). Subjects who were heterozygous (arginine/proline) at codon 25 had a significantly higher (P= 0.04) gingival overgrowth score than those who were homozygous for arginine. Logistic regression analysis indicated that for codon 25 independent predictors of severe gingival overgrowth were the heterozygous arginine/proline genotype (P= 0.009) and whether the individual was young (P= 0.05).
  
  
  CONCLUSIONS
  Polymorphisms in the TGF-beta1 gene influence the expression of gingival overgrowth in renal transplant recipients concomitantly treated with cyclosporin and a calcium channel blocker. The polymorphism in the TGF-beta1 gene at codon 25 represented an independent genetic determinant of severe gingival overgrowth in the susceptible subjects studied.
authors.affiliation: Division of Restorative Dentistry, School of Dentistry, Queen's University of Belfast, UK. g.linden@qub.ac.uk
authors.forename: G J
authors.initials: GJ
authors.lastname: Linden
authors.forename: S E
authors.initials: SE
authors.lastname: Haworth
authors.forename: A P
authors.initials: AP
authors.lastname: Maxwell
authors.forename: K V
authors.initials: KV
authors.lastname: Poulton
authors.forename: P A
authors.initials: PA
authors.lastname: Dyer
authors.forename: D
authors.initials: D
authors.lastname: Middleton
authors.forename: C R
authors.initials: CR
authors.lastname: Irwin
authors.forename: J J
authors.initials: JJ
authors.lastname: Marley
authors.forename: P
authors.initials: P
authors.lastname: McNamee
authors.forename: C D
authors.initials: CD
authors.lastname: Short
authors.forename: P S
authors.initials: PS
authors.lastname: Hull
authors.forename: J A
authors.initials: JA
authors.lastname: James
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D000704:Analysis of Variance; D001120:Arginine / Q000235:genetics; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D016009:Chi-Square Distribution; D003062:Codon / Q000235:genetics; D016001:Confidence Intervals; D016572:Cyclosporine / Q000009:adverse effects*; D004247:DNA / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000145:classification* / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation; D007930:Leucine / Q000235:genetics; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011392:Proline / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
chemical_list: D002121:Calcium Channel Blockers; D003062:Codon; D007166:Immunosuppressive Agents; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D004247:DNA; D001120:Arginine; D011392:Proline; D007930:Leucine