CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment

Figures & data

Table 1 Allele frequency of CYP2C9 *2 and CYP2C9 *3 in normal volunteers

Study	Number of cases	Country population	*2 frequency (%)	*3 frequency (%)
Soga et al^Citation29	56	Japanese	0	5.4
Nasu et al^Citation84	218	Japanese	0	2.1
Wang et al^Citation85	115	Han Chinese	0	1.7
Sullivan-Klose et al^Citation30	100	Caucasian Americans	8.0	6.0
	100	African-Americans	1.0	0.5
	98	Taiwanese	0	1.7
Stubbins et al^Citation34	100	Caucasian British	12.5	8.5
Hamdy et al^Citation42	247	Egyptians	12.0	6.0
Aynacioglu et al^Citation37	499	Turks	10.6	10.0
Brockmöller et al^Citation32	174	Germans	13	8.1
Yasar et al^Citation38	430	Swedish	10.7	7.4
Vianna-Jorge et al^Citation43	331	Brazilians	8.6	6.5
Jose et al^Citation44	346	Indians (South)	4	8
Scordo et al^Citation39	157	Italians	11.2	9.2
Kimura et al^Citation36	140	Japanese	0	3.6
Yoon et al^Citation40	574	Koreans	0	1.1
Gaedigk et al^Citation41	153	Canadians	3	6
Sánchez-Diz et al^Citation46	1076	Spanish and Italians	12.5–16.5	7.1–8.5
Scott et al^Citation45	250	US Ashkenazi Jews	14	8.6

Table 2 Allele frequency of CYP2C9 *2 and CYP2C9 *3 in patients with epilepsy

Study	Number of cases	Country population	*2 frequency (%)	*3 frequency (%)
Hashimoto et al^Citation86	17	Japanese	0	11.8
Odani et al^Citation87	44	Japanese	0	13.6
Soga et al^Citation29	28	Japanese	0	10.7
Twardowschy et al^Citation88	100	Brazilians	9	7.0
Chaudhary et al^Citation60	89	Indians	4.5	10.1

Table 3 Phenytoin metabolic changes comparing both CYP2C9 wild-type and mutant variants

Study	N	Methods	Results of mutant variants versus wild-type variant	P value
Rosemary et al^Citation9	27	300 mg PHT, 4 h after intake	Double ↑ BL-PHT in the presence of mutant alleles	0.01
Kerb et al^Citation89	96	300 mg PHT, 12 h after intake	1 mutant allele = ↑ 31% BL-PHT	<0.0001
			2 mutant alleles = ↑ 52% BL-PHT
Aynacioglu et al^Citation37	101	300 mg PHT, 12 h after intake	*1/*2 = ↑ 32% BL-PHT	0.009
			*1/*3 = ↑ 35% BL-PHT	0.001
			*2/*2 = ↑ 58% BL-PHT	0.02
			*3/*3 = ↑ 42% BL-PHT	Not calculated
Soga et al^Citation29	28	Chronic use, 2 h after intake	*1/*3 = ↑ 58% ratio C/D	0.01
Hung et al^Citation8	169	Chronic use, average daily PHT dose of 293.64 ± 75.20 mg/kg/day	*1/*1 CYP2C9 + C19 (mutant) = ↓ 20% Cl	<0.05
			*1/*3 CYP2C9 + C19 (mutant) = ↓ 50% Cl	<0.05
Ozkaynakci et al^Citation90	102	Chronic use, average daily PHT dose of 4.13 ± 1.07 mg/kg/day	Mean BL-PHT: Group CYP2C9 *1/*3 + CYP2C19 *2/*3 = 27.95 ± 1.85 µg/mL (highest)	<0.001
			Mean BL-PHT: Group CYP2C9 *1/*1 + CYP2C19 *1/*1 = 7.43 ± 0.73 µg/mL (lowest)

Abbreviations: N, number of patients; PHT, phenytoin; BL-PHT, blood level of phenytoin; C/D, serum phenytoin concentration/dose of phenytoin; Cl, clearance of phenytoin.

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