P‐glycoprotein drug transporter MDR1 gene polymorphism in renal transplant patients with and without gingival overgrowth

Abstract

To determine whether there is association between genotypes of drug transporter multidrug resistant (MDR)1 gene coding drug transporter P-glycoprotein and gingival overgrowth in kidney transplant patients. Fifty-four unrelated kidney transplant patients suffering from gingival overgrowth as well 120 control transplant patients without overgrowth were enrolled into the study. Gingival overgrowth was assessed by two independent periodontal specialists at 6 months after transplantation. During the post-transplant period all patients were given medication, which included cyclosporine A, diltiazem or verapamil, prednisone, azathioprine. MDR1 C3435T polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism assay. In kidney transplant patients suffering from gingival overgrowth mean score of gingival overgrowth was 1.43 +/- 0.63, whereas in control subjects was 0.0. Patients with gingival overgrowth induced by immunosuppressive medication were characterized by similar distribution of MDR1 genotypes. There were no significant differences of 3435CC, 20.4% and 22.5%, 3435CT, 61.1% and 54.2% and 3435TT, 18.5% and 23.3% genotypes (frequencies) between patients with and without gingival overgrowth. The risk of gingival overgrowth was the highest among patients carrying 3435CT genotype (OD 1.33), but did not differ markedly from the other genotypes, i.e. 3435CC (OD 0.88) and 3435TT (OD 0.75). Likewise to genotypes, distribution of alleles was similar in patients with gingival overgrowth and healthy gingiva. The wild-type allele 3435C was found in 50.9% and 49.6% of subjects whereas the mutated allele 3435T was revealed in 49.1% and 50.4% of patients with and without gingival overgrowth, respectively. The evaluated risk of gingival overgrowth in patients with 3435C allele was 1.06 versus 0.95 in those with healthy gingiva. The medication regimen administered in both groups of the study was comparable. Immunohistochemical studies revealed expression of P-glycoprotein in ducts of the salivary gland. No association between the MDR1 gene polymorphism and gingival overgrowth was revealed in kidney transplant patients administered cyclosporine A as a principal immunosuppressive agent. Further studies are needed to elucidate the role of P-glycoprotein in drug transport in salivary glands.