Cytochrome P450 2C9 gene polymorphism in phenytoin induced gingival enlargement: A case report

Abstract

Gingival enlargement comprises any clinical condition in which an increase in the size of the gingiva is observed. Among the drugs that induce gingival enlargement, the antiepileptic agent phenytoin has been widely related to this condition. The Cytochrome P450(CYP) superfamily is the most commonly involved enzymes in metabolism of drugs. Common coding region CYP variants that affects drug elimination and response has been studied in great detail. Pharmacogenetic influences on drug metabolism have been widely reviewed and gene polymorphism of cytochrome P450 2C9 appeared to be responsible for much of the interindividual variability on drug elimination. Genetic variation in the CYP2C9 gene can affect metabolism, leading to altered phenotypes. Individuals with poor metaboliser alleles of CYP2C9 gene were shown to have a reduced metabolism of phenytoin compared with wild-type alleles. Thus identification of patients genotype prior to anti-epileptic drug administration could potentially prevent higher serum drug concentrations leading to adverse side effects such as gingival enlargement. This case report addresses the influence of CYP2C9 genetic polymorphism on Phenytoin drug metabolism thereby causing gingival enlargement.

Drug-induced gingival overgrowth: A critical insight into case reports from over two decades

“…Reported cases of gingival enlargements were induced by different drugs; CCBs (50/119 – of which amlodipine-25;[8910111213141516171819202122232425262728] nifedipine-13;[26293031323334353637383940] verapamil-4;[41] felodipine-2;[4243] nisoldipine-1;[44] manidipine-1;[45] and unspecified CCBs-4[46]); phenytoin (11/119);[4748495051525354555657] cyclosporine (31/119);[3546585960616263646566676869707172737475] phenobarbital (4/119);[767778] sodium valproate (3/119 - including one report of congenital drug-induced gingival hyperplasia);[798081] d-penicillamine (2/119);[82] combination oral contraceptive pill-lynestrenol and ethinyl estradiol (1/119);[83] vigabatrin (1/119). [84] Cases of gingival enlargement after combination drug therapy have also been reported; a combination of cyclosporine and CCBs (11/119);[354685...…”

“…Babu et al . in 2013[47] evaluated drug metabolizing enzyme cytochrome P450 2C9 gene polymorphism in an epileptic patient under phenytoin therapy who presented with generalized gingival enlargement. The pharmacogenomic study of the patient revealed that the patient was a homozygous mutant of CYP2C9 which prompted them to substitute the drug.…”

Presence of a single nucleotide polymorphism (RS3758581) in a boy with DRESS syndrome

“…It is estimated that about 19% of patients taking phenytoin develop hypersensitivity reactions [ 8 ]. Not all patients taking phenytoin develop phenytoin-induced severe cutaneous adverse reactions such as DRESS, Steven-Johnson syndrome and toxic epidermal necrolysis [ 12 ]. Evidence suggests that genetic factors also might have a significant role in the pathogenesis of phenytoin-induced severe cutaneous adverse reactions [ 8 , 12 - 17 ].…”

“…Genetic variation in the CYP2C9 gene can affect the metabolism, leading to altered phenotypes. It was discovered that CYP2C9 gene polymorphisms known to cause a 93% to 95% reduction in phenytoin clearance are important genetic factors for phenytoin-related severe cutaneous adverse reactions [ 8 , 12 - 16 ]. To investigate the genetic factors associated with phenytoin-related DRESS syndrome, we carried out a genome-wide association study, followed by direct sequencing of the associated gene and replication analyses.…”

Multidrug resistance 1 gene polymorphism in amlodipine-induced gingival enlargement

“…Evidence suggests that genetic factors also might have a significant role in the pathogenesis of gingival enlargement and the patient's susceptibility to this unwanted effect. [ 10 11 ] A genetic predisposition could influence a variety of factors in the drug plaque-induced inflammation. These include gingival fibroblast functional heterogeneity, collagenolytic activity, drug metabolism, and collagen synthesis.…”