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首页> 外文期刊>Clinical Pharmacology and Therapeutics >MDR1 gene polymorphisms and risk of gingival hyperplasia induced by calcium antagonists.
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MDR1 gene polymorphisms and risk of gingival hyperplasia induced by calcium antagonists.

机译：MDR1基因多态性和钙拮抗剂诱导的牙龈增生的风险。

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BACKGROUND: Gingival overgrowth is a common side effect of calcium antagonists. Although the pathogenesis is unknown, several lines of evidence point to a modulation of inflammatory processes. Because the calcium antagonists, albeit to a variable degree, act as inhibitors of P-glycoprotein (P-gp), the gene product of multidrug resistance 1 (MDR1), and inflammation may modify P-gp expression, we analyzed the MDR1 polymorphisms as risk factors for gingival overgrowth induced by calcium antagonists. METHODS: Clinical, laboratory, and anamnestic data including periodontal parameters and use of calcium antagonists were assessed in a cross-sectional epidemiologic investigation (N = 1484). MDR1 polymorphisms in exon 21 G2677T/A and exon 26 C3435T were determined. P-gp expression was detected in gingival tissues. In a matched-pair analysis, 93 subjects using calcium antagonists and 186 not using them were compared. RESULTS: P-gp is expressed in the endothelial layers of blood vessels obtained from healthy or inflamed gingiva. Subjects treated with calcium antagonists had significantly deeper gingival pockets than their drug-free counterparts (P <.0001). This drug-related side effect was associated with the MDR1 2677G/G or G/TA genotype (P <.001) but not with the variant genotype T/TA. This drug effect was proved by multiple regression analysis with adjustment for the risk factors of periodontitis (age, sex, smoking, and education) (P <.0001) and was associated with elevated C-reactive protein levels. The association of probing depth with the MDR1 polymorphism was confirmed in the matched-pair analysis (P <.0001). CONCLUSION: Treatment with calcium antagonists leads to gingival hyperplasia, which is associated with the MDR1 G2677T/A polymorphism. The MDR1 genotype may modify the inflammatory response to the drugs.
机译：背景：牙龈过度生长是钙拮抗剂的常见副作用。尽管其发病机理尚不清楚，但有几条证据表明炎症过程有所调节。由于钙拮抗剂在不同程度上可作为P-糖蛋白（P-gp），多药抗性1（MDR1）的基因产物和炎症可能会改变P-gp表达的抑制剂，因此我们将MDR1多态性分析为钙拮抗剂引起牙龈过度生长的危险因素。方法：在横断面流行病学调查中评估了临床，实验室和记忆删除数据，包括牙周参数和钙拮抗剂的使用（N = 1484）。确定了外显子21 G2677T / A和外显子26 C3435T中的MDR1多态性。在牙龈组织中检测到P-gp表达。在配对分析中，比较了93位使用钙拮抗剂的受试者和186位未使用钙拮抗剂的受试者。结果：P-gp在从健康或发炎的牙龈得到的血管内皮层中表达。用钙拮抗剂治疗的受试者比没有药物治疗的受试者具有更深的牙龈袋（P <.0001）。这种与药物有关的副作用与MDR1 2677G / G或G / TA基因型相关（P <.001），但与变异基因型T / TA不相关。通过对牙周炎危险因素（年龄，性别，吸烟和受教育程度）进行调整的多元回归分析证明了这种药物作用（P <.0001），并且与C反应蛋白水平升高有关。在配对分析中证实了探测深度与MDR1多态性的关联（P <.0001）。结论：钙拮抗剂治疗导致牙龈增生，这与MDR1 G2677T / A多态性有关。 MDR1基因型可能会改变对药物的炎症反应。

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