Apoptosis and expression of caspase-3 in cyclosporin-induced gingival overgrowth

BACKGROUND: The pathogenesis of epithelial thickening in gingival overgrowth remains obscure. Apoptosis plays an important role in maintaining tissue hemostasis. The aim of the present study was to investigate apoptosis via immunohistochemical analyses in cyclosporin A-induced gingival overgrowth tissue samples to determine whether these processes play a role in the pathogenesis of gingival overgrowth. METHODS: Gingival biopsies (one per person) were harvested from 22 renal transplant recipients (eight men and 14 women; mean age, 36.4 +/- 13.3 years) who had been diagnosed with cyclosporin A-induced gingival enlargement and from 12 systemically healthy persons (seven men and five women; mean age, 27.0 +/- 16.0 years) with plaque-induced gingivitis. Distributions of caspase-3 and apoptosis were determined immunologically. RESULTS: Significant differences were found with regard to caspase-3 levels and the extent of apoptosis between the cyclosporin A group and the control group. Plaque index, gingival index, and probing depths were significantly lower in the control group. CONCLUSION: The extent of keratinocyte apoptosis and decreased levels of caspase-3 may be an important factor affecting the gingiva of kidney transplant recipients with cyclosporin A-induced gingival overgrowth.     

Cyclosporin associated gingival overgrowth in renal transplant recipients

OBJECTIVES: To investigate the prevalence and severity of gingival overgrowth in a group of renal transplant recipients treated in one centre in Northern Ireland. STUDY DESIGN: A consecutive group of patients who had had a renal transplant for at least 6 months and were attending the Renal Unit in Belfast City Hospital took part in the study. These were divided into a group of 84 subjects treated with cyclosporin since their transplant who were compared with a control group of 36 transplant recipients who had never received cyclosporin. Each subject had a periodontal examination and completed a questionnaire. The severity of gingival overgrowth was scored from plaster models. OUTCOME MEASURES: Clinically significant gingival overgrowth was equated with a score of > or = 30 using the index developed by Seymour et al (1985). RESULTS: 41 (49%) of the cyclosporin group had clinically significant gingival overgrowth compared with none of the controls. A significantly higher proportion of males had overgrowth than females. There were significant correlations between age at transplant, plaque, bleeding, pocketing and the severity of gingival overgrowth. Many patients with clinically significant gingival overgrowth were apparently unconcerned about this condition. CONCLUSIONS: It is concluded that gingival overgrowth is a significant problem for renal transplant patients treated with cyclosporin, particularly if they are also treated with a calcium channel blocker. None of the factors measured, in isolation, explained the variable expression of gingival overgrowth in those at risk.     

The effect of a plaque control programme on the incidence and severity of cyclosporin-induced gingival changes

The efficacy of plaque control as a means of preventing cyclosporin-induced gingival overgrowth was assessed in 27 adult renal transplant patients. After baseline examination, patients were randomly allocated to receive intensive oral hygiene instructions, scaling and root planing (OH group) or no treatment (no treatment group). Gingival condition was assessed 6 months after baseline and changes in gingival form were related to various periodontal and pharmacokinetic measures. In both treatment groups, there was a significant increase (P less than 0.05) in gingival hyperplasia scores at 6 months. In the OH group, plaque scores were significantly lower (P less than 0.05) at 6 months, whereas in the no treatment group, a significant increase in plaque scores, gingival inflammation and probing depths was observed at 6 months. Dosages of cyclosporin, whole blood concentrations of cyclosporin, baseline gingival index, hyperplasia scores, and 6-month plaque index were not important determinants for the increase in gingival over-growth in both treatment groups. It is concluded that attention to plaque control and the removal of local irritants is of some benefit for the gingival health of cyclosporin-treated adult renal transplant patients, but these measures alone did not prevent gingival overgrowth. Pharmacokinetic variables of cyclosporin and various periodontal measures were not good predictors of cyclosporin-induced gingival changes.     

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.     

The calcium channel blocker used with cyclosporin has an effect on gingival overgrowth

BACKGROUND/AIMS: To investigate whether the choice of calcium channel blocker, used in conjunction with cyclosporin A, affected the prevalence of gingival overgrowth. METHOD: A cohort of 135 renal transplant recipients who had been medicated with cyclosporin A in combination with either nifedipine (89) or amlodipine (46) since transplant, took part in the study. The inclusion criteria were that eligible subjects had been in receipt of a kidney transplant for at least 12 months, had at least 10 teeth and had not received specialist periodontal treatment. The age, gender, current drug regimen and dosage were recorded for each participant and alginate impressions taken of both arches. The presence and severity of gingival overgrowth were scored from plaster models. RESULTS: A higher proportion (72%) of the amlodipine group were categorised as having gingival overgrowth compared with only 53% of the nifedipine group, chi square=4.5, p<0.05. Logistic regression analysis was used to explore the relationship between the presence or absence of gingival overgrowth (dependent variable) and age, gender, time since transplant, dose of cyclosporin A, centre in which the patient was treated, and the calcium channel blocker used (independent variables). Independent predictors of gingival overgrowth in this multivariate analysis were whether the individual was treated with amlodipine or nifedipine (p=0.01) and whether the individual was young or old (p=0.01). Within the multivariate analysis, the odds ratio for amlodipine to be associated with gingival overgrowth compared with nifedipine was 3.0 (confidence interval 1.3-6.9). CONCLUSIONS: The prevalence of gingival overgrowth in renal transplant recipients maintained on cyclosporin A and nifedipine is lower than those treated with cyclosporin A and amlodipine.     

Marginal periodontium as a potential reservoir of human papillomavirus in oral mucosa

BACKGROUND: Although human papillomaviruses (HPVs) are associated with a number of proliferative epithelial lesions including squamous cell malignancies, they can also be detected in the normal oral mucosa in 10% to 20% of the adult population. However, the point of entry and the site of replication of HPV in the oral cavity are not known. Since the gingival pocket is the only site in the oral mucosa where basal cells, known to be targets of HPV at other mucosal sites, are normally exposed to the environment, we hypothesized that this could be the site of latent HPV. METHODS: Gingival biopsies taken from 38 individuals with clinically diagnosed periodontal disease were examined. The presence of HPV DNA was studied by using nested PCR (polymerase chain reaction with MY09/MY11 and GP05+/GP06+ primers targeting the L1 region of HPV), followed by subsequent hybridization with a cocktail of 12 high-risk HPV oligoprobes and in situ hybridization (ISH) with probes for HPV screening and the HPV subtype 16. RESULTS: In the present study, high-risk HPV types were detected in 26% (8/31) of the gingival biopsies with PCR. By using in situ hybridization, the viral DNA was localized to the coronal part of the junctional epithelium in the gingival pocket. CONCLUSIONS: The results suggest that the periodontal pocket might serve as a reservoir of HPVs in oral mucosa. While having important implications in understanding the HPV transmission, this observation does not rule out the possibility that HPV may be involved in the initiation of periodontal disease.     

肾移植患者龈下菌群状况对牙龈增生的影响

目的了解肾移植患者牙周及龈下菌群状况，探索环胞素A（cyclosporine A，CsA）引起的牙龈增生的影响因素。方法肾移植患者20例，用CsA药前、后3个月和6个月分别记录龈下产黑菌数量和厌氧菌总量，以及菌斑指数、出血指数、探诊深度和牙龈增生指数等各项牙周指标，进行统计分析。结果用CsA药后3个月及6个月细菌数量较用药前均有明显增加，牙周炎症也明显加重，用药后6个月牙龈增生出现，以上差异均有统计学意义（P〈0．05）。细菌数量与牙龈增生指数具有相关性（P〈0．01）。结论龈下细菌数量是肾移植患者应用CsA引起牙龈增生的重要影响因素，提示肾移植患者在术前和术后应加强牙周检查及治疗。     

Tacrolimus is not associated with gingival overgrowth in renal transplant patients

BACKGROUND: Cyclosporin A is used extensively to prevent the rejection of allogenic renal transplants. However, it is associated with a variety of undesirable side effects including gingival overgrowth. Tacrolimus (FK506), has been marketed as an effective alternative immunosuppressant to cyclosporin A and recent subjective reports suggest patients taking it complain infrequently of gingival problems. This clinical investigation was undertaken to confirm whether or not tacrolimus adversely affected the gingival health of renal transplant recipients. METHODS: Renal transplant patients (RTPs) under the care of the Renal Transplantation Service at the Manchester Royal Infirmary, who had received a renal allograft at least 18 months earlier, were recruited for this study. All but one of the RTPs had been taking tacrolimus since transplantation. The other had commenced tacrolimus therapy two months after receiving her allograft. A hospital based control group was recruited from non transplanted individuals attending the Turner Dental School, Manchester. Each patient underwent a detailed dental assessment and had dental impressions taken. The extent of gingival overgrowth was determined from plaster models. RESULTS: 25 renal transplant recipients and 26 control patients were included in the study. None of the individuals in either the tacrolimus or control groups had clinically significant overgrowth. The patients in the tacrolimus group with the highest overgrowth scores were those also taking calcium antagonists as treatment for hypertension. CONCLUSION: This study demonstrates that tacrolimus has no adverse effects on the gingival tissues and thus has potential as an alternative immunosuppressant for individuals susceptible to developing cyclosporin A-induced gingival overgrowth.     

Gingival fibroblasts grown from cyclosporin-treated patients show a reduced production of matrix metalloproteinase-1 (MMP-1) compared with normal gingival fibroblasts, and cyclosporin down-regulates the production of MMP-1 stimulated by pro-inflammatory cytokines

BACKGROUND AND OBJECTIVE: Cyclosporin-induced gingival overgrowth arises from an alteration in collagen homeostasis and is enhanced by inflammatory changes in the gingival tissues. The aim of this study was to investigate the interaction among interleukin-1, oncostatin M, cyclosporin and nifedipine in promoting the up-regulation of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase by gingival fibroblasts. MATERIAL AND METHODS: Fibroblast cultures (n = 5) were obtained from healthy controls and from patients with cyclosporin-induced gingival overgrowth, and cells were harvested between the fourth and ninth passages. Cells were stimulated with interleukin-1 and oncostatin M, alone or in combination, and with different concentrations of cyclosporin (0-2000 ng/mL) and nifedipine (0-200 ng/mL). MMP-1 and tissue inhibitor of metalloproteinase-1 production was determined using an enzyme-linked immunosorbent assay technique. A CyQuant cell proliferation assay was used to determine the DNA concentration in the sample. RESULTS: Fibroblasts obtained from patients with cyclosporin-induced gingival overgrowth produced significantly lower levels of MMP-1 than control fibroblasts (p < 0.001); tissue inhibitor of metalloproteinase-1 levels were significantly lower (p < 0.05), and the ratio of MMP-1 to tissue inhibitor of metalloproteinase-1 was reduced, in the conditioned medium of patients with cyclosporin-induced gingival overgrowth compared with controls. Interleukin-1 and oncostatin M produced a significant increase in the up-regulation of MMP-1, which was reversed when cyclosporin and nifedipine were added to the cell cultures (p < 0.05). CONCLUSION: Pro-inflammatory cytokines significantly up-regulate MMP-1 in cultured gingival fibroblasts. Up-regulation is attenuated by both cyclosporin and nifedipine. The interaction may account for the synergism between inflammation and cyclosporin-induced gingival overgrowth.     

Two different human papillomavirus (HPV) types associated with oral mucosal lesions in an HIV-seropositive man

Different types of Human papillomaviruses (HPV) are associated with a variety of oral lesions. So far, HPV types 1, 2, 4, 6, 7, 11, 13, 16, 18, 32 and 57 have been identified in oral lesions. Immunosuppression predisposes oral mucosa to clinical manifestation of different virus infections including HPV. We describe here a 30-year-old HIV-positive and immunosuppressed man, who had suffered from oral lesions for a few months. On clinical examination, a nodular elevation was detected on the lower lip, and white keratotic areas were present on buccal mucosa bilaterally. A biopsy from the lip revealed the presence of acanthosis with a prominent granular cell layer as well as hyperparakeratosis. A biopsy from the buccal lesion showed a comparatively much flatter lesion with merely basal cell hyperplasia associated with hyperparakeratosis. Koilocytosis was a characteristic feature in both biopsies. In Southern blot hybridization, both lesions hybridized with a probe cocktail comprising HPV 6, 11, 16, 18, 31 and 33 DNA under low stringency. Under high stringency, the lip lesion proved to contain HPV 7 DNA, which also confirmed by in situ hybridization. The buccal lesion was weakly positive by Southern blot with HPV 11 and 13 probes hybridized under stringent conditions, but the restriction patterns with Pst I and Bam HI did not fit with those of any of the 57 HPV types known so far. In situ hybridizations with HPV 11 and HPV 13 probes were negative. Cloning of this 'new' HPV type is currently under way.     

Stereologic study of cyclosporin A-induced gingival overgrowth in renal transplant patients

Gingival biopsies were taken from 13 renal transplant patients (mean age 26.5 yr), 11 of whom exhibited cyclosporin A (CsA)-inditced gingival overgrowth. Control material was obtained from seven volunteers (mean age 28 yr). Gingival tissue components were analyzed by quantitative microscopy (stereology) on 5-(μm-thick sections of interdental papillae. The volume density (Vv) of different tissue components and the surface density of epithelial ridges were calculated by conventional point and intersection counting. The study showed that the volume density of oral epithelium and the surface density of the epithelial ridges in the CsA-induced gingival overgrowth were significantly increased compared to normal gingival tissue. The connective tissue of the lesion exhibited a significant increase in volume density of cells, blood vessels and non-collagenous matrix with a corresponding decrease in the collagenous matrix. These results indicate that CsA-induced gingival overgrowth represents a tissue with an altered composition characterized by increased thickness of oral epithelium and relatively-increased amount of cells, vessels, non-collagenous matrix and decreased collagenous matrix in the connective tissue.     

The prevalence and severity of cyclosporin and nifedipine-induced gingival overgrowth

Abstract The gingival health of 32 renal transplant patients who were medicated with cyclosporin was compared with a similar cohort of 23 renal transplant patients medicated with both cyclosporin and nifedipine. Both groups of patients had been taking the above medication for at least 3 months. Plaque scores, gingival inflammation and probing depths were similar for both groups. Patients medicated with the combination of nifedipine and cyclosporin had a significantly higher gingival overgrowth score (p= <0.046) when compared with the group receiving cyclosporin alone. The incidence of clinically significant overgrowth (i.e., overgrowth >30% which would require surgical intervention) was similar in both groups. Gingival overgrowth was not related to cyclosporin dosage. It is concluded that patients taking cyclosporin or cyclosporin and nifedipine experience gingival overgrowth and that the severity of the overgrowth is greater in patients taking the combined therapy. The levels of plaque and gingival inflammation appear to be associated with this phenomenon.     

Expression of fibronectin-binding integrins in gingival epithelium in drug-induced gingival overgrowth

BACKGROUND AND OBJECTIVE: Gingival overgrowth is a side-effect of nifedipine and cyclosporin medications. Integrins are transmembrane glycoproteins that mediate cell adhesion, regulate cell proliferation and participate in the regulation of tissue fibrosis. The aim of this study was to investigate whether expression of epithelial cell integrins is linked to the development of drug-induced gingival overgrowth. MATERIAL AND METHODS: Human gingival biopsies of patients taking nifedipine, cyclosporin, or a combination of both medications, were used. Expression of the alpha5beta1, alphavbeta1 and alphavbeta6 integrins, and of cellular extra domain A of fibronectin, was localized in frozen sections using immunohistochemistry. RESULTS: The activated conformation of the beta1, alpha5beta1 and alphavbeta6 integrins were more frequently expressed in distinct locations in the oral epithelium in the combined drug group. Cellular extra domain A of fibronectin, a ligand for both alpha5beta1 and alphavbeta6 integrins, was expressed within the connective tissue of all groups. It was also expressed around the basal keratinocytes of the control, nifedipine and cyclosporin-induced gingival overgrowth groups, but not in the combined medication group. No relationship between the presence of inflammation and integrin expression was found. CONCLUSION: The results indicate that expression of certain integrins is up-regulated in the epithelium of drug-induced gingival overgrowth where they could participate in controlling the formation of elongated rete ridges and tissue fibrosis.     

Epidermal growth factor in saliva and serum of patients with cyclosporin-induced gingival overgrowth

The purpose of this study was to investigate the presence of epidermal growth factor (EGF) in patients receiving cyclosporin therapy who had gingival overgrowth and to determine whether there were any differences between these patients and normal healthy controls. Seventeen patients with cyclosporin-induced gingival overgrowth and seventeen age- and sex-matched controls who were taking cyclosporin but had healthy gingiva were used for this study. Unstimulated whole saliva was collected from all individuals by expectoration. Gingival crevicular fluid (GCF) was also collected from all individuals. Blood was additionally collected from all subjects and serum was separated by keeping the samples overnight at 4 degrees C. EGF levels in all cases were measured by an ELISA assay. EGF concentrations were found to be significantly higher in the saliva of patients with cyclosporin-induced gingival overgrowth compared to the control group (401.2 +/- 31.1 pg/ml and 144.3 +/- 31.4 pg/ml, respectively), whereas the results were reversed in the serum (67.0 +/- 15.6 pg/ml and 141.6 +/- 17.7 pg/ml, respectively). EGF was not detected in the samples of GCF in either group. This study thus demonstrated an increase in EGF levels in the saliva and a decrease of EGF in the serum of patients with cyclosporin-induced gingival overgrowth.     

Demographic, pharmacologic, and periodontal variables for gingival overgrowth in subjects medicated with cyclosporin in the absence of calcium channel blockers

BACKGROUND: The role of cyclosporin in the absence of calcium channel blockers and the associated risk variables of development and severity of gingival overgrowth have not yet been properly established. The present study was conducted to determine the effect of potential risk variables for gingival overgrowth severity in Brazilian renal transplant subjects medicated with cyclosporin in the absence of any calcium channel blockers. METHODS: A cross-sectional study was conducted in a public hospital in Belo Horizonte, Brazil. Demographic, pharmacologic, and periodontal data, recorded from 194 subjects taking cyclosporin in the absence of calcium channel blockers, were analyzed using independent sample t, chi2 statistic, or Mann-Whitney U tests. The effects of potential risk variables of gingival overgrowth severity were determined using backward stepwise regression analysis. RESULTS: The prevalence of clinically significant gingival overgrowth was 34.5% (N = 67). These subjects presented a significantly higher papillary bleeding index and a higher plaque index compared to those without clinically significant gingival overgrowth. When all demographic, pharmacologic, and periodontal data were evaluated in relation to gingival overgrowth severity, time since transplant, papillary bleeding index, serum cyclosporin concentration, and prednisolone and azathioprine dosages were significant in the univariate modeling (P <0.05) and remained significant when evaluated in the multivariate modeling (P <0.0001; adjusted R2 = 39.4%). CONCLUSIONS: In the absence of calcium channel blockers, this study showed that pharmacologic variables, such as cyclosporin serum concentration, prednisolone and azathioprine dosages, and time since transplant, are strongly related to gingival overgrowth. In addition, the periodontal variable papillary bleeding index highlighted the primary role of inflammation on the pathogenesis and severity of gingival overgrowth.     

In situ detection of human papillomavirus Types 13 and 32 in focal epithelial hyperplasia of the oral mucosa

17 cases of focal epithelial hyperplasia of the oral mucosa (FEH, Heck's disease) were investigated for the presence of human papillomavirus (HPV) nucleic acid sequences by means of in situ DNA hybridization using biotinylated DNA probes of HPV types 1, 6, 11, 13, 16, 18, and 32. Ten of 17 cases were positive for HPV 13 DNA in contrast to 6 of 17 positive cases obtained after application of the HPV 32 probe, with a double infection in one case. The results of our study suggest, that HPV 13 and HPV 32 are very specifically found in lesions of FEH and can be detected in a high percentage of cases using in situ hybridization.     

Oral health in renal transplant recipients administered cyclosporin A or tacrolimus

OBJECTIVE: The aim of this study was to determine the oral status of renal transplant recipients receiving cyclosporin A (CsA) or tacrolimus (FK-506) as immunosuppressant. SUBJECTS AND METHODS: A total of 88 renal transplant recipients receiving CsA (63 men and 25 women, mean age 51.4 years) and 67 receiving FK-506 (57 men and 10 women, mean age 33.5 years) were included in the study. Donor type, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Demographics and pharmacological data were recorded for all subjects. RESULTS: The results demonstrated that CsA caused a greater number of oral diseases. A greater number of gingival overgrowth was present in patients treated with CsA. However, the combined use with calcium channel blockers increased the gingival overgrowth number. The occurrence of candida in saliva was observed in 80 renal recipients treated with CsA and 20 treated with FK-506. The presence of squamous oral carcinoma (n = 3) and herpes simplex (n = 10) was observed in patients treated with CsA. These alterations were not observed in renal recipients treated with FK-506. CONCLUSIONS: Renal recipients constitute a high-risk group for oral diseases, as they are immunocompromised. However, the FK-506 regime appears to ameliorate this effect, compared with CsA. Adequate pre- and post-transplant oral health care is recommended for these subjects, irrespective of the time interval for which the drug is administered.     

Crevicular fluid levels of TGFbeta1 in drug-induced gingival overgrowth

OBJECTIVE: To determine if local, gingival crevicular fluid (GCF) levels of TGFbeta1 were altered in drug-induced gingival overgrowth. Patients and methods: GCF samples were collected on Periopaper strips from 45 renal transplant recipients who had been medicated with cyclosporin or cyclosporin in combination with other putative overgrowth-inducing drugs for a minimum of 6 months. Twenty-two subjects had gingival overgrowth while the other 23 patients showed no signs of gingival changes and constituted the medicated control group. Non-medicated controls consisted 20 periodontally healthy individuals who had never taken overgrowth-inducing drugs. GCF levels of TGFbeta1 and alkaline phosphatase, a marker of inflammation, were determined by enhanced chemiluminescence ELISA and enzyme activity assays, respectively. RESULTS: TGFbeta1 levels in GCF from overgrowth and non-overgrowth sites in overgrowth sufferers did not differ. However, there were significant differences in median concentration (P = 0.001) and GCF levels of TGFbeta1 per sample (P = 0.05) between study groups with overgrowth patients having higher amounts per sample and lower concentrations than medicated and healthy controls. Median levels of alkaline phosphatase per GCF sample differed between site (P = 0.01) with higher levels present at overgrowth sites. Despite this, the concentration of enzyme in GCF did not differ between site or patient group. CONCLUSIONS: GCF TGFbeta1 detected in overgrowth patients could reflect a higher level of gingival inflammation because of difficulties in plaque control consequent on the development of overgrowth. However, the higher local levels of total TGFbeta1 in overgrowth patients could indicate that it is a risk factor for developing gingival overgrowth.     

TGF-β1 gene polymorphism in renal transplant patients with and without gingival overgrowth

Oral Diseases (2011) 17 , 414–419 Background: The incidence of gingival overgrowth among renal transplant patients treated with cyclosporine A ranges from 13% to 84.6%, and the overgrowth is not only esthetic but also a medical problem. We studied the determination of association between TGF‐β1 (TGFB1) gene polymorphism and gingival overgrowth in kidney transplant patients medicated with cyclosporin A. Methods: Eighty‐four kidney transplant patients with gingival overgrowth and 140 control transplant patients without overgrowth were enrolled into the case control study. TGFB1 polymorphism was determined using the PCR‐RFLP assay for +869T>C in codon 10 and +915G>C in codon 25 as well as TaqMan real‐time PCR assays for promoter ?800G>A and ?509C>T SNPs. Results: In kidney transplant patients suffering from gingival overgrowth, mean score of gingival overgrowth was 1.38 ± 0.60, whereas in control subjects it was 0.0. The patients with gingival overgrowth were characterized by similar distribution of TGFB1 genotypes and allele in comparison to subjects without gingival overgrowth. Among 16 potentially possible haplotypes of TGFB1 gene, only four were observed in the studied sample of kidney transplant patients: G_C_T_G, G_T_C_G, G_C_C_C, and A_C_T_G, with similar frequency in patients with and without gingival overgrowth. Conclusion: No association between the TGFB1 gene polymorphism and gingival overgrowth was revealed in kidney transplant patients administered cyclosporine A.