Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S‐mephenytoin

  title={Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S‐mephenytoin},
  author={Leif Bertilsson and Ya-qing Lou and Y L Du and Yin Liu and Tang‐Yun Kuang and Xia‐Mau Liao and Ke‐Yi Wang and Jes{\'u}s Reviriego and Lennart Iselius and Folke Sj{\"o}qvist},
  journal={Clinical Pharmacology \& Therapeutics},
The frequency of poor metabolizers of debrisoquin was low and similar in four different native Chinese nationalities. In a total sample of 695 Chinese subjects, only seven (1.01%) had a urinary ratio between debrisoquin and 4‐hydroxydebrisoquin >12.6, which is the antimode between poor metabolizers and extensive metabolizers in white populations. This is significantly lower than the 6.82% found in 1011 white Swedish healthy subjects (p < 0.0001). Admixture analysis indicated the occurrence of… 
Debrisoquine and S -mephenytoin hydroxylation polymorphisms in a Russian population living in Estonia
The frequencies of poor metabolisers of debrisoquine and S-mephenytoin among Russians were similar to those in other Caucasian populations studied so far.
Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele.
Ratios of urinary S/R-mephenytoin in homozygous EMs were lower than those of heterozygously EMs for both Han and Bai subjects, which shows a gene-dosage effect.
Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: Polymorphism in RFLP and DNA sequence of CYP2D6
The C/T188,G/A1934, G/C4268, and RFLP polymorphisms may explain the interracial variations between Chinese and white subjects, as well as the genetic variations among Chinese subjects.
Debrisoquin and S-mephenytoin hydroxylation phenotypes and CYP2D6 genotypes in an Estonian population.
The distribution of genetically determined metabolic capacities of CYP 2D6 and CYP2C19 in Estonian unrelated subjects did not differ significantly from that in other Caucasian populations.
A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity.
It is postulated that the CYP2D6*17 allele might contribute to the molecular basis of the previously established diminished debrisoquine hydroxylase activity in African Bantu populations.
Proguanil metabolism is determined by the mephenytoin oxidation polymorphism in Vietnamese living in Denmark.
There was no statistically significant correlation (Spearmans rs) between any index of proguanil metabolism and the sparteine metabolic ratio and the urinary S/R-mephenytoin ratio.
Debrisoquine 4-hydroxylase (CYP2D6) genetic polymorphisms and susceptibility to schizophrenia in Chinese patients from Taiwan
The data suggest that the CYP2D6 gene may not be a susceptibility gene for schizophrenia in Chinese schizophrenic patients, and it is suggested that the 1934A allele is very rare in Chinese.
Differences in the Incidence of the CYP 2 C 19 Polymorphism Affecting the S-Mephenytoin Phenotype in Chinese Han and Bai Populations and Identification of a New Rare CYP 2 C 19 Mutant Allele 1
The incidence of the S-mephenytoin polymorphism was compared in two Chinese ethnic groups, Han and Bai, by phenotype and genotype analysis and it was found that Han subjects may be more susceptible than Bai subjects to the drugs metabolized by the CYP2C19 enzyme.


Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations
Interethnic differences in debrisoquin and mephenytoin hydroxylation have been compared between normal white (n = 183) and Japanese (n = 100) subjects with the 8‐hour urinary metaboUc ratio of
Metoprolol and mephenytoin oxidation polymorphisms in Far Eastern Oriental subjects: Japanese versus mainland Chinese
The findings indicate that the two Far Eastern Oriental subject groups have a lower frequency of PM phenotype of debrisoquin/sparteine‐type oxidation and a greater incidence ofPM phenotype of mephenytoin oxidation compared with the respective frequencies reported from white subjects.
Diazepam metabolism in native Chinese poor and extensive hydroxylators of S‐mephenytoin: Interethnic differences in comparison with white subjects
The metabolism of diazepam was slow in both extensive metabolizers and poor metabolizers of mephenytoin among Chinese subjects and similar to that in white subjects who were poor metabolizer, which indicates that there are interethnic differences not only in the incidence of poor metabolization of me pheny toin but also in the substrate specificity of the S‐mephenytoin hydroxylase.
Polymorphic debrisoquin hydroxylation in 757 Swedish subjects
The calculated frequency of the single allele that is believed to control deficient debrisoquin hydroxylation is similar among white Swedish people, as among other white groups examined so far; however, it is significantly different from the frequency in certain Oriental groups.
Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine hydroxylation in a Swedish population
In the Swedish population studied, allele‐specific PCR amplification allowed prediction of the debrisoquin hydroxylation phenotype with 99% accuracy.
Mephenytoin hydroxylation deficiency in Caucasians: Frequency of a new oxidative drug metabolism polymorphism
The ability of normal subjects to hydroxylate mephenytoin or debrisoquine after oral dosing was investigated in 156 unrelated Caucasians living in middle Tennessee, and it is suggested that 4‐hydroxylation of mephenYtoin is a new polymorphism independent of that for debrisquine.
Debrisoquin oxidation polymorphism in a Spanish population
The capacity for debrisoquin metabolism was determined in 377 healthy Spanish volunteers by measuring the amount of debrisoquin and its main metabolite, 4‐hydroxydebrisoquin, in urine after an oral
Importance of genetic factors in the regulation of diazepam metabolism: Relationship to S‐mephenytoin, but not debrisoquin, hydroxylation phenotype
The metabolism of both diazepam and demethyldiazepam is related to the mephenytoin, but not to the debrisoquin, hydroxylation phenotype, and there was no significant difference in volume of distribution of the benzodiazepines between the phenotypes.
The mephenytoin oxidation polymorphism is partially responsible for the N‐demethylation of imipramine
In conclusion, this and an earlier study show that the oxidation of imipramine is mediated by means of two different polymorphic P450 isozymes, 2‐hydroxylation by way of the sparteine oxygenase (P450IID6) and demethylation by Way of the mephenytoin oxygen enzyme (P 450IIC8).
Propranolol's metabolism is determined by both mephenytoin and debrisoquin hydroxylase activities
Two independent isozymes of cytochrome P‐450, previously identified as being responsible for debrisoquin and S‐mephenytoin hydroxylation, contribute to the two separate oxidative routes of metabolism of propranolol.