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.
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.
Linden
G J
GJ
Division of Restorative Dentistry, School of Dentistry, Queen's University of Belfast, UK. g.linden@qub.ac.uk
Haworth
S E
SE
Maxwell
A P
AP
Poulton
K V
KV
Dyer
P A
PA
Middleton
D
D
Irwin
C R
CR
Marley
J J
JJ
McNamee
P
P
Short
C D
CD
Hull
P S
PS
James
J A
JA
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
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