MDR1 gene polymorphisms and risk of gingival hyperplasia induced by calcium antagonists.

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.

• 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)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Calcium Channel Blockers

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