Possible association of CTLA-4 gene polymorphism with cyclosporine-induced gingival Overgrowth in kidney transplant recipients

T-lymphocytes may play a role in the pathogenesis of inflammatory periodontal diseases and cyclosporine (CsA)-induced gingival overgrowth (GO). The gene encoding CTLA-4 (Cytotoxic T-lymphocyte antigen 4, a molecule influencing T-cell activation), is known to have a single nucleotide polymorphism (SNP) in promoter C > T -318; an exon 1 A > G 49, and a microsatellite dinucleotide repeat polymorphism (AT) in exon 4. The purpose of this study was to analyze the possible influence of polymorphisms of CTLA-4, interleukin (IL)-2, and tumor necrosis factor (TNF)-alpha on GO incidence in eighty two renal transplant recipients. 34 CsA-treated with significant GO (CsAGO+); 22, CsA-treated with no GO (CsAGO-), and 26 tacrolimus (Tac)-treated without GO (TacGO-). The SNPs of CTLA-4 (-318 C > T and +49 A > G), IL-2 (-330T > G), and TNF-alpha (-308 G > A) were determined by SSP-PCR methods. The CTLA-4 (AT) genotype was determined using polymerase chain reaction and fluorescence-based analysis with capillary electrophoresis. Allele frequencies in all patient groups were similar for CTLA-4 -318C > T, IL-2, and TNF-a. However, patients with CsAGO+ showed differences from CsAGO- for allele and genotype frequencies in position +49A > G of the CTLA-4 gene. The +49G allele was two times less frequent among CsAGO+ than CsAGO- (P =.0052; P corrected =.008). Slight differences between CsAGO+ and CsAGO- were noticed for the genotype distribution of CTLA-4 (AT) (P =.056). The results suggested that appearance of an adenosine allele(A) in position +49 of the CTLA-4 gene may be a permissive element for CsA-induced GO.