Examination of α2 Integrin Polymorphism in Drug-induced Gingival Overgrowth : α2 Integrin+1648 G/A Polymorphism

Abstract

Drug-induced gingival overgrowth is a side effect observed in patients taking calcium channel blockers, anti-epileptic drugs or immunosuppressant drugs. Some reports had showed different mechanisms for the incidence of gingival overgrowth, and we recently showed that gingival overgrowth was caused by collagen accumulation via drug-induced inhibition of α2 integrin expression and collagen phagocytosis in gingival fibroblasts. However, the reason for the difference in the incidence of gingival overgrowth in the reports was unclear. Single polymorphism (SNP) is known to be a hereditary factor associated with the incidence of some diseases. We showed that α2 integrin +807C/T polymorphism was correlated to the incidence of gingival overgrowth, but was not directly related to that induction because +807C/T polymorphism does not result in the change of amino acid sequence, suggesting that other SNP near the +807 site may cooperatively affect the incidence of gingival overgrowth. In the present study, we investigated the association between incidence of gingival overgrowth and α2 integrin +1648 G/A polymorphism, which is a linkage disequilibrium for +807C/T. The subjects were 98 patients who took calcium channel blockers, phenytoin or cyclosporin A. Gingival overgrowth was evaluated by the standard of McGaw et al.. Peripheral blood samples were collected from 45 subjects with gingival overgrowth (case group) and 53 subjects without it (control group). Genome DNA was extracted from blood and the α2 integrin +1648 site was analyzed by sequencing. The genotype distribution of the +1648 G/A polymorphism showed that GG genotype was highly present in 95.6% and 88.7% of the case and control groups, respectively, and GA genotype was 4.4% and 9.4%, respectively, and AA genotype occurred in only one subject in the control group. The frequency of the +1648 G allele was 97.8% and 94.7% in the case and control groups, respectively, and that of the +1648 A allele was 2.2% and 5.3%. Significant differences were not observed between the two groups. This result suggests that the incidence of drug-induced gingival overgrowth is not associated with human α2 integrin +1648 G/A polymorphism, but may be associated with a cooperation of +807C/T and other than + 1648 G/A polymorphism.