METHOD: The main polymorphisms on the cytochrome P450 (CYP) genes, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, and the multi-drug resistance 1 gene (MDR1) were genotyped in 78 healthy Vietnamese subjects. Pharmacokinetic metrics were available for CYP2A6 (coumarin), CYP2C19 (mephenytoin), CYP2D6 (metoprolol) and CYP3As (midazolam), allowing correlations with the determined genotype.
RESULTS: In the CYP2 family, we detected alleles CYP2A6*4 (12%) and *5 (15%); CYP2B6*4 (8%), *6 (27%); CYP2C19*2 (31%) and *3 (6%); CYP2D6*4, *5, *10 (1, 8 and 44%, respectively). In the CYP3A family, CYP3A4*1B was detected at a low frequency (2%), whereas CYP3A5 *3 was detected at a frequency of 67%. The MDR1 3435T allele was present with a prevalence of 40%. Allele proportions in our cohort were compared with those reported for other Asian populations. CYP2C19 genotypes were associated to the S-4'-OH-mephenytoin/S-mephenytoin ratio quantified in plasma 4 h after intake of 100 mg mephenytoin. While CYP2D6 genotypes were partially reflected by the alpha-OH-metroprolol/metoprolol ratio in plasma 4 h after dosing, no correlation existed between midazolam plasma concentrations 4 h post-dose and CYP3A genotypes.
CONCLUSIONS: The Vietnamese subjects of our study cohort presented allele prevalences in drug-metabolising enzymes that were generally comparable with those reported in other Asian populations. Deviations were found for CYP2A6*4 compared to a Chinese population (12 vs. 5%, respectively; P = 0.023), CYP2A6*5 compared with a Korean population (15 vs. <1%, respectively; P < 0.0001), a Malaysian population (1%; P < 0.0001) and a Chinese population (1%; P < 0.0001); CYP2B6*6 compared with a Korean population (27 vs. 12%; P = 0.002) and a Japanese population (16%; P = 0.021). Pharmacokinetic metrics versus genotype analysis reinforces the view that the predictive value of certain globally common variants (e.g. CYP2D6 single nucleotide polymorphisms) should be evaluated in a population-specific manner.
METHODS: Stimuli were presented in both monocular and dichoptic conditions at eight visual field locations/eye. The incommensurate stimulus frequencies ranged from 15.45 to 21.51 Hz. Five stimulus conditions differing in spatial frequency and orientation were examined for three viewing conditions. The resulting 15 stimulus conditions were examined in 16 normal subjects who repeated all conditions twice.
RESULTS: Several significant independent effects were identified. Response amplitudes were reduced for dichoptic viewing (by 0.85 times, p<4 x 10(-11)); offset by increases in responses for between eye differences of one octave of spatial frequency: lower (1.15 times, 0.1 cpd); higher (1.29 times, 0.4 cpd), both p<1.8 x 10(-7). Crossed orientations produced significant effects upon response phase (p=0.023) but not amplitude (p=0.062).
CONCLUSIONS: The results indicated that dichoptic evoked potentials using multifocal frequency-doubling illusion stimuli are practical. The use of crossed orientation, or differing spatial frequencies, in the two eyes reduced binocular interactions.
SIGNIFICANCE: The results indicate a method wherein several spatial or temporal and frequencies per visual field region can be tested in reasonable time using a multifocal VEP using spatial frequency-doubling stimuli.