Drozdzik M, Mysliwiec K, Lewinska-Chelstowska M, Banach J, Drozdzik A, Grabarek J
Department of Pharmacology, Pomeranian Medical University, Poland.
J Clin Periodontol. 2004 Sep;31(9):758-63. doi: 10.1111/j.1600-051x.2004.00554.x.
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.
确定编码药物转运蛋白P-糖蛋白的药物转运体多药耐药（MDR）1基因的基因型与肾移植患者牙龈增生之间是否存在关联。
54例患有牙龈增生的非亲属肾移植患者以及120例无牙龈增生的对照移植患者纳入本研究。移植后6个月由两名独立的牙周专科医生评估牙龈增生情况。移植后期间所有患者均接受药物治疗，包括环孢素A、地尔硫䓬或维拉帕米、泼尼松、硫唑嘌呤。采用聚合酶链反应-限制性片段长度多态性分析确定MDR1 C3435T多态性。
患有牙龈增生的肾移植患者牙龈增生平均评分为1.¬43±0.¬63，而对照组为0.¬0。免疫抑制药物所致牙龈增生患者的MDR1基因型分布相似。有牙龈增生和无牙龈增生患者之间的3435CC基因型（频率）分别为20.¬4%和22.¬5%、3435CT基因型（频率）分别为61.¬1%和54.¬2%、3435TT基因型（频率）分别为18.¬5%和23.¬3%，无显著差异。携带3435CT基因型的患者牙龈增生风险最高（比值比1.¬33），但与其他基因型即3435CC（比值比0.¬88）和3435TT（比值比0.¬75）相比无明显差异。与基因型情况相同，有牙龈增生患者和牙龈健康患者的等位基因分布相似。野生型等位基因3435C分别在50.¬9%和49.¬6%的受试者中发现，而突变等位基因3435T分别在有和无牙龈增生患者中的比例为49.¬1%和50.¬4%。3435C等位基因患者的牙龈增生评估风险为1.¬06，而牙龈健康者为0.¬95。研究两组患者的用药方案具有可比性。免疫组织化学研究显示唾液腺导管中有P-糖蛋白表达。
在以环孢素A作为主要免疫抑制剂的肾移植患者中，未发现MDR1基因多态性与牙龈增生之间存在关联。需要进一步研究以阐明P-糖蛋白在唾液腺药物转运中的作用。
