The influence of transforming growth factor-β1 gene polymorphisms on the severity of gingival overgrowth associated with concomitant use of cyclosporin a and a calcium channel blocker

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)β1 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-β1 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-β1 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-β1 gene at codon 25 represented an independent genetic determinant of severe gingival overgrowth in the susceptible subjects studied.