Abstract | 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.
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Authors | Peter Meisel, Jürgen Giebel, Christiane Kunert-Keil, Peter Dazert, Heyo K Kroemer, Thomas Kocher |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 79
Issue 1
Pg. 62-71
(Jan 2006)
ISSN: 0009-9236 [Print] United States |
PMID | 16413242
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Calcium Channel Blockers
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(biosynthesis, genetics)
- Adult
- Aging
(physiology)
- Calcium Channel Blockers
(adverse effects)
- Endothelium, Vascular
(pathology)
- Exons
(genetics)
- Female
- Gene Frequency
- Genes, MDR
(genetics)
- Genotype
- Germany
(epidemiology)
- Gingiva
(pathology)
- Gingival Hyperplasia
(chemically induced, epidemiology, pathology)
- Humans
- Immunohistochemistry
- Male
- Middle Aged
- Polymorphism, Genetic
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- Risk Factors
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