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S L Huang

Publications and source records attributed to S L Huang.

At least 73 records · Page 4Linked to original sources
PubMed1998

Effect of antisense mitogen-activated protein kinase oligonucleotides on rat vascular smooth muscle cell proliferation induced by EGF in vitro.

AIM: To study the preventive effect of down-regulating mitogen-activated protein kinase (MAPK) on vascular smooth muscle cell (VSMC) proliferation. METHODS: Cultured rat VSMC was pretreated with a phosphorothioate-protected 17-mer antisense MAPK oligodeoxynucleotides (ODN) directed against the initiation of translation sites of the p42- and p44-MAPK isoforms by liposomal transfection. A 17-mer sense and a random sequence MAPK ODN were used as control. After liposomal transfection, cells were exposed to epidermal growth factor (EGF) 1 nmol.L-1 for 10 min and then harvested in lysis buffer. MAPK activity was measured by Western blot and P-81 phosphocellulose filter papers method by using [gamma-32P] ATP and myelin basic protein as substrate. DNA synthesis was measured by [3H]thymidine incorporation. RESULTS: Antisense ODN 0.2 mumol.L-1 reduced EGF-induced MAPK activities by 84%, and inhibited VSMC [3H]thymidine incorporation stimulated by EGF. CONCLUSION: A 17-mer MAPK antisense oligonucleotide directed against the initiation of translation sites of the p44- and p42-MAPK inhibited EGF-stimulated rat VSMC proliferation.

Animals↗
PubMed1998

Determination of S/R ratio of mephenytoin in human urine by chiral HPLC and ultraviolet detection and its comparison with gas chromatography.

AIM: To improve HPLC method for rapid determination of urinary S/R-ratio of mephenytoin, a widely used metabolic index for cytochrome P-450 2C19 (CYP2C19) activity. METHODS: Aliquots of 0-8-h urine sample after dosing racemic mephenytoin 100 mg underwent one-step extraction with dichloromethane. Analysis was performed on a chiral column (250 mm x 4 mm, 5 microns) at lambda = 207 nm. The eluent was a mixture of acetronitrile and water containing both 0.1% glacial acetic acid and 0.2% triethylamine (14:86, vol/vol) at a flow-rate of 0.9 mL.min-1. RESULTS: The enatiomers of mephenytoin in urine were well separated within 9 min. A linear correlation was observed between 50-5000 micrograms.L-1 with the detection limit of 12.5 micrograms.L-1 for both enantiomers of mephenytoin. This HPLC analysis was comparable to gas chromatography in accuracy and sensitivity, but with much shorter retention time and better resolution. CONCLUSION: The present HPLC method is good for rapid determination of the ability of subjects to hydroxylate S-mephenytoin after oral administration of the racemic drug.

Aryl Hydrocarbon Hydroxylases↗
PubMed1998

Cytochrome P450 1A1 MspI polymorphism and urinary 1-hydroxypyrene concentrations in coke-oven workers.

Coke-oven workers are regularly exposed to a high concentration of the benzene-soluble fraction (BSF) of total particulates, which are comprised mainly of polycyclic aromatic hydrocarbons (PAHs). A metabolite of pyrene, 1-hydroxpyrene (1-OHP), is readily measured in the urine of exposed individuals. Epidemiological studies have shown that P4501A1 (CYP1A1) genotypes are associated with PAH-related lung cancer risk. The purpose of this study was to investigate whether CYP1A1 MspI genotypes modulate the relationship of individual occupational exposure to air BSF to urinary 1-OHP concentrations among coke-oven workers. We monitored individual breathing zone air BSF over 3 consecutive days in 80 coke-oven workers in Taiwan from August 1995 to February 1996. Exposure was also dichotomized by work area (topside oven workers and sideoven workers). Preshift urine on the morning of day 1 and postshift urine on the afternoon of day 3 were measured by fluorescent spectrophotometry, and blood samples were analyzed to determine the relative distributions of CYP1A1 MspI polymorphisms. The frequency of the MspI homozygous variant genotypes of CYP1A1 was 15%. Multiple linear regression showed significant effects of individual occupational exposure to air BSF and preshift 1-OHP on postshift urinary 1-OHP concentrations (P = 0.002 and P < 0.001, respectively). After adjusting for preshift 1-OHP concentrations and air BSF, subjects with the homozygous variant genotype have a 2-fold higher postshift 1-OHP levels than the combined wild-type and heterozygous (P = 0.04). In addition, a positive trend was found in postshift 1-OHP and across-shift change of 1-OHP (postshift 1-OHP - preshift 1-OHP) in decreasing order, as follows: topside oven workers with the homozygous variant trait, topside oven workers with the heterozygous variant trait, sideoven workers with the homozygous variant trait, and sideoven workers with the heterozygous trait (P < 0.001). We conclude that CYP1A1 MspI variant genotype can modify the metabolism of PAHs in coke-oven workers.

Adult↗
PubMed1998

Implications of a failed prospective trial of adjuvant therapy after radical hysterectomy for stage Ib-IIa cervical carcinoma with pelvic node metastases.

BACKGROUND: Lymph node metastasis is established as a poor prognostic factor in cervical carcinoma patients undergoing primary surgery. However the optimal postoperative therapy for node-positive patients remains to be defined. MATERIALS AND METHODS: To determine the role of adjuvant therapy in stage Ib-IIa cervical carcinoma patients who had pelvic node metastases after radical hysterectomy, a single institutional randomized controlled trial with factorial design, comparing concurrent chemo-radiotherapy (CT + RT) versus chemotherapy (CT) or radiotherapy (RT) alone was conducted. Study endpoints included site of recurrence, time to recurrence, relapse-free and overall survivals, and toxicity of treatment. RESULTS: At a median follow-up of 61 months, the 6-year relapse-free and overall survival rates of the 39 patients entered into this trial were 78.2% and 85.2%, respectively. This trial was prematurely closed due to suboptimal accrual and protocol violation. It is inconclusive regarding the efficacy of CT because of the limitation of the sample size and the imbalance of prognostic features by actual treatment. A model for risk group classification of patients with stage Ib-II cervical carcinoma with pelvic node metastases from a retrospective analysis was validated by this prospective cohort. The results of this failed trial suggest that adjuvant CT alone seemed comparable to RT alone or CT + RT in survival but was associated with significantly less morbidity. CONCLUSION: It is warranted to consider a CT alone arm in comparison with either observation or CT + RT according to risk of recurrence in future prospective trials. However, this important issue can only be addressed by a large multicenter trial.

Adult↗
PubMed1997

A 346-base pair region of the mouse gamma-glutamyl transpeptidase type II promoter contains sufficient cis-acting elements for kidney-restricted expression in transgenic mice.

The mouse gamma-glutamyl transpeptidase (GGT) gene encodes seven distinct mRNAs that are transcribed from seven separate promoters. Type II mRNA is the most abundant in kidney. We have developed a cell line with features of renal proximal tubular cells which expresses GGT mRNA types with a pattern similar to that of mouse kidney. Because a 346-bp sequence from the type II promoter directed the highest level of CAT activity in these cells, this region was used to drive the expression of a beta-galactosidase reporter gene in transgenic mice. Two transgenic mouse lines expressed beta-galactosidase limited to the renal proximal tubules. Site-directed deletions within this 346-bp promoter region demonstrated that cis-elements containing the consensus binding sites for AP2, a glucocorticoid response element (GRE)-like element, and the initiator region were required for transcriptional activity and were not additive. Purified AP2 bound and footprinted the AP2 consensus region, making it likely that transcription from the GGT type II promoter is regulated in part by AP2. These data suggest that transcription of the type II promoter requires multiple protein DNA interactions involving at least an AP2 element, and probably a GRE-like element and the initiator region.

Animals↗
PubMed1997

Effect of troleandomycin on the pharmacokinetics of imipramine in Chinese: the role of CYP3A.

AIMS: In vitro data indicate that imipramine (IMI), a widely used tricyclic antidepressant drug, is N-demethylated by several isoforms of cytochrome P450, which include CYP3A4. The aim of this study was to investigate the role of CYP3A in the in vivo N-demethylation of IMI. METHODS: Healthy subjects were given troleandomycin (TAO), a selective inhibitor of CYP3A, 250 mg daily for 2 days before a single oral dose of 100 mg IMI was administered. RESULTS: Pretreatment with TAO significantly increased the AUC of IMI by 59% (1971 +/- 938 vs 3134 +/- 2000 microg l(-1) h, 95% confidence interval for difference between means: 218 to 2108 microg l(-1) h, P < 0.05) and decreased its oral clearance by 30% (60.9 +/- 27.4 vs 42.5 +/- 22.7 l h(-1), 95% confidence internal for difference between means: 7.2 to 31.7 l h(-1), P < 0.05). CONCLUSIONS: We conclude that CYP3A may play an important role in the in vivo N-demethylation of IMI.

Adult↗
PubMed1997

Evidence for the effect of gender on activity of (S)-mephenytoin 4'-hydroxylase (CYP2C19) in a Chinese population.

There is evidence that the sex-dependent expression of individual forms of the human cytochrome P450s (CYPs) results in gender-related differences in the hepatic metabolism of certain drugs. Previous work has shown that conflicting evidence exists relating to the sex differences in the activity of (S)-mephenytoin 4'-hydroxylase (CYP2C19). Accordingly, we assessed the effect of gender on CYP2C19 activity in a phenotyped and genotyped healthy unrelated Chinese population for further evidence of such a gender-based differentiation. One hundred and sixteen females and 129 males took one tablet of 100 mg racemic mephenytoin (Mesantoin, Sandoz) after emptying their urinary bladders. Amounts of (S)- and (R)-mephenytoin and its metabolite 4'-hydroxymephenytoin (4'-OH-M) excreted in the postdose 0-8 h urine collection were determined by GC and HPLC methods, respectively. The CYP2C19 activity was expressed as the ratio of S/R-mephenytoin (S/R-ratio), the percentage of the dose excreted as 4'-OH-M (D%), and the log10 of the hydroxylation index which was defined as the ratio of micromoles of (S)-mephenytoin dose to micromoles of 4'-OH-M excreted in urine (1g HI). From all the subjects studied, 53 extensive metabolizers (EMs) and 19 poor metabolizers (PMs) phenotyped were randomly selected and the DNA extracted from their blood samples was utilized for genotyping analysis according to the previously developed standard procedures. In this population, the phenotype PMs were identified in 10.9% (14/128) of the males, as compared with 11.2% (13/116) of the females (chi 2 = 0.0045, df = 1; p > 0.05). In all phenotyped subjects, the S/R-ratio of EM males was significantly higher than that of EM females (mean +/- SD; 0.28 +/- 0.17 vs. 0.24 +/- 0.15; p = 0.030), but no sexual differentiation was observed (p > 0.05) in 4'-OH-M excreted among all EMs and PMs, or the S/R-ratio among all PMs. In all genotyped EMs, the frequency of homozygous EMs was 18.4% higher in females (51.7%, 15/29) than in males (33.3%, 8/24) although there was no significant difference (chi 2 = 1.1370, df = 1, p > 0.05), but the S/R-ratio was lower in homozygous females than in homozygous males (0.22 +/- 0.14 vs. 0.33 +/- 0.09; p = 0.046). Thus, we conclude that the higher CYP2C19 activity in females exists among both the phenotyped EMs and the genotyped homozygous EMs compared with that in males, and that the defect frequency of the enzyme activity is equal between the genders. We also conclude that the S/R-ratio is more a sensitive metabolic marker of CYP2C19 enzyme activity than the D% and 1g HI.

Adolescent↗
PubMed1997

Meta-analysis of phenotype and genotype of NAT2 deficiency in Chinese populations.

Data on both the incidence of slow acetylator phenotype of probe drugs isoniazid, sulfadimidine or sulfamethazine, caffeine and dapsone in mainland or overseas Chinese, and the distribution of NAT2 genotypes and the frequency of NAT2 alleles in the Chinese populations were summarized and reanalysed using a meta-analysis method. Frequency of the slow acetylator phenotype in 3516 healthy Han Chinese gave an overall mean of approximately 19.9 +/- 4.0%, with the range of the combined data being between 15.8% and 25.5%. In addition, frequencies of the slow acetylator phenotype differ between the different minorities in Chinese populations and the range was between 3.2% and 50.6%, with a mean value of 20.6 +/- 12.9% in a total of 1842 individuals from 17 Chinese minorities. In addition, there was no significant heterogeneity in overseas Chinese between the probe drugs isoniazid and sulfadimidine or sulfamethazine (chi 2 = 5.97, df = 4; p > 0.05), and the mean value of slow acetylator phenotype incidence was 24.5% (119/485; 95% CI: 20.7-28.3%), consistent with that of the native Chinese. As expected, frequency of the slow acetylator genotypes in Chinese populations was 25.4% (112/441; 95% CI: 21.3-29.5%), which was in accordance with that of the slow acetylator phenotype in native or overseas Chinese. For all genotypes, *4/*4 (29.9%, 132/441), *4/*6A (27.4%, 121/441), *4/*7A (12%, 53/441) and *6A/*6A (11.3%, 50/441) occupied 80.6%, but *5A/*7A (0.2%, 1/441), *5A/*5A (1.1%, 5/441) and *7A/*7A (1.8%, 8/441) were not frequently found. From this report, the genotype frequencies of homozygous rapid acetylator, heterozygous rapid acetylator, and homozygous slow acetylator were found to be 0.299 (132/441), 0.447 (197/441) and 0.254 (112/441), respectively. Furthermore, both *4 (52.3%; 95% CI: 49-56%) and *6A (30.5%; 95% CI: 28-34%) were major NAT2 alleles, while *7A (11.2%; 95% CI: 9-13%) and *5A (6%; 95% CI: 4-8%) were uncommonly present. Frequency of the mutant alleles was observed at 0.477 (421/882 alleles). The *7A constituted 23.5% t(99/421) of slow acetylator alleles in Chinese populations, showing that this point mutation exists not only in Oriental or Asiatic, but also in Chinese populations. According to the Hardy-Weinberg equilibrium, in the phenotyped Chinese populations, the mean estimate of predicted allelic frequencies of the genotypes RR, Rr, and rr was 0.294, 0.496, and 0.210 for the Chinese, and the expected frequency of the deficient gene r was 0.458. By comparison, the predicted values are in complete agreement with the observed ones. In conclusion, this meta-analysis determined the accurate population frequencies of phenotype and genotype of the NAT2 genetic deficiency in healthy Chinese subjects.

Arylamine N-Acetyltransferase↗
PubMed1997

Tumor necrosis factor-alpha gene polymorphism in chronic bronchitis.

Airway inflammation is an important pathologic feature in chronic bronchitis, and we hypothesized that individuals with greater inflammatory responses may be more likely to acquire the disease. A polymorphism at -308 position of the tumor necrosis factor-alpha (TNF-alpha) gene has been described, with the rarer allele, TNF2, demonstrated to have higher inducibility in vitro. We investigated the distribution of this polymorphism in a case-control study. The genotype was determined in 42 male patients with chronic bronchitis, 42 sex-, age-, and smoking index-matched control subjects, and 99 random-sampled schoolchildren. We report here that the TNF2 allele is overrepresented in the patient group. The allele frequency of TNF2 is 5.1% in the schoolchildren, 2.4% in the control group, and 19% in the bronchitis group (p < 0.01). Carriage of the TNF2 allele confers a higher risk to the development of chronic bronchitis (odds ratio = 11.1, 95% CI = 2.89-42.57). The results demonstrate the important pathologic role of TNF-alpha in chronic bronchitis and suggest that greater inflammatory response may predispose an individual to this disease.

Aged↗
PubMed1997

No correlation between side-chain of propranolol oxidation and S-mephenytoin 4'-hydroxylase activity.

AIM: To determine if any correlation between the side-chain oxidative capacity for propranolol and S-mephenytoin 4'-hydroxylase (cytochrome P-450 2C19, CYP2C19) activity in healthy Chinese of Han nationality. METHODS: S-mephenytoin oxidative metabolite 4'-hydroxymephenytoin (4'OH-M), S- and R-mephenytoin, and naphthoxyl-actic acid (NLA) excreted in urine, and propranolol in plasma were measured after 14 healthy extensive metabolizers of S-mephenytoin oxidation were given a single oral dose of racemic mephenytoin 100 mg and racemic propranolol 80 mg, respectively. S/R-mephenytoin in urine was determined by chiral capillary gas chromatography with nitrogen-phosphorus detection, 4'-OH-M in urine by reversed-phase liquid chromatography (RPLC) with ultraviolet detection, and plasma propranolol or urinary NLA by the RPLC with fluorescence detection. RESULTS: No significant correlations were found between the partial metabolic clearance (Clm) of propranolol to NLA and 8 h urinary S/R ratio of mephenytoin (rs = -0.0484; P = 0.8695), nor between the Clm and log10 of 8 h urinary excretion of 4'-OH-M (rs = -0.1077; P = 0.7140). CONCLUSIONS: CYP2C19 is not a principal P-450 isozyme responsible for the in vivo side-chain oxidation of propranolol in the Chinese.

Aryl Hydrocarbon Hydroxylases↗
PubMed1997

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.

The incidence of the S-mephenytoin polymorphism was compared in two Chinese ethnic groups, Han (n = 101) and Bai (n = 202) by phenotype and genotype analysis. The frequency of poor metabolizers (PMs) in Han vs. Bai subjects was 19.8% vs. 13.4%. Han subjects had a higher frequency of the mutant CYP2C19m1 allele (0.366 vs. 0.257, P < .01) and a lower frequency of the wild-type allele (0.559 vs. 0.688, P < .01) than Bai subjects, which is consistent with the difference in the frequencies of PMs between the two ethnic groups. This results in a lower percentage of homozygous wild-type extensive metabolizers of mephenytoin (EMs) in Han subjects than in Bai subjects (40% vs. 59%, P = .005). Therefore, Han subjects may be more susceptible than Bai subjects to the drugs metabolized by the CYP2C19 enzyme. Ratios of urinary S/R-mephenytoin in homozygous EMs were lower than those of heterozygous EMs for both Han and Bai subjects, which shows a gene-dosage effect. Genotype analysis identified all but one PM as homozygous or heterozygous for the two known mutant CYP2C19m1 and/or CYP2C19m2 alleles. A single Bai PM outlier was shown to be heterozygous for CYP2C19m1 and a new mutant CYP2C19 allele containing a single amino acid change of Arg433 --> Trp433. A genotyping test demonstrated that only this one individual carried this rare allele (frequency of 0.0025 in Bai subjects).

Alleles↗
PubMed1997

Comparison of major aeroallergens in Taipei and Kin-Men.

Ragweed pollen is an important aeroallergen in the USA, however, its role in the pathogenesis of allergic airway diseases in Taiwan has not been reported. Recently, a dramatic increase in patients with allergic rhinitis was noted in Kin-Men. Most patients had characteristic seasonal variation with the symptoms waxing in August and waning in November, which correlated with the pollen season of ragweed. The aim of this study was to clarify the role of ragweed pollen in the pathogenesis of allergic airway disease in Taipei and Kin-Men. Ragweed pollen from Kin-Men was collected, extracted, and resuspended in phosphate-buffered saline for a skin prick test. Greer ragweed pollen extract was used as a control. Serum from patients with a positive skin test was investigated for the ragweed pollen-specific immunoglobulin E (IgE). The IgE-binding components in the ragweed pollen were determined using immunoblot analysis. Of 101 patients from Kin-Men, 79 responded to ragweed. Only eight of 117 patients from Taipei responded to the same allergen. The titers of ragweed-specific IgE antibodies in the sera from Kin-Men were much higher than in the sera from Taipei. The response rate to the most common indoor allergen, Dermatophagoides pteronyssinus, was much lower in Kin-Men than in Taipei (25.7% and 90.6%, respectively). Thus, there were different aeroallergens in Kin-Men and Taipei. Having what was in both cases a Chinese population affected by different allergens indicates that environmental allergens may play an important role in the pathogenesis of allergic airway diseases. These results may also serve as a reference for the prophylaxis of allergic rhinitis in Kin-Men.

Adolescent↗
PubMed1997

[Clinical application of modified proportional unit of middle finger to determine the depth for intra-esophageal atrial pacing to stop supraventricular tachycardia].

OBJECTIVE: To determine the location for catheter electrode of intra-esophageal atrial pacing. METHODS: The catheter load was placed at a length eleven times that of the modified proportional unit of middle finger for intra-esophageal atrial pacing to stop the supraventricular tachycardia of 21 patients. RESULTS: Ninteen of them showed remarkable effect and 2 were effective. Tachycardia of all the patients was stopped, symptoms and signs such as chest distress, palpitation relieved and the blood pressure normalized. CONCLUSION: This is an accurate localization, rapid, convenient method with remarkable effects, it is a new way in rescuing supraventricular tachycardia patients.

Adolescent↗
PubMed1996

Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice.

gamma-Glutamyl transpeptidase (GGT) is an ectoenzyme that catalyzes the first step in the cleavage of glutathione (GSH) and plays an essential role in the metabolism of GSH and GSH conjugates of carcinogens, toxins, and eicosanoids. To learn more about the role of GGT in metabolism in vivo, we used embryonic stem cell technology to generate GGT-deficient (GGTm1/GGTm1) mice. GGT-deficient mice appear normal at birth but grow slowly and by 6 weeks are about half the weight of wild-type mice. They are sexually immature, develop cataracts, and have coats with a gray cast. Most die between 10 and 18 weeks. Plasma and urine GSH levels in the GGTm1/GGTm1 mice are elevated 6-fold and 2500-fold, respectively, compared with wild-type mice. Tissue GSH levels are markedly reduced in eye, liver, and pancreas. Plasma cyst(e)ine levels in GGTm1/GGTm1 mice are reduced to approximately 20% of wild-type mice. Oral administration of N-acetylcysteine to GGTm1/GGTm1 mice results in normal growth rates and partially restores the normal agouti coat color. These findings demonstrate the importance of GGT and the gamma-glutamyl cycle in cysteine and GSH homeostasis.

Animals↗
PubMed1996

Induction, not associated with host-cell re-activation of damaged plasmid DNA, of damaged-DNA-recognition proteins by retinoic acid and dibutyryl cyclic AMP in mammalian cells.

Our previous studies [Chao (1992) Biochem. J. 282, 203-207; C.C.-K. Chao, unpublished work] has suggested a correlation between the levels of constitutive UV-damaged-DNA-recognitionproteins (UVDRP) and cellular DNA repair in different cell types. In the present study, UVDRP were induced in F9 and NIH3T3 cells by 0.1 microM retinoic acid (RA) and 1 mM dibutyryl cyclic AMP (dbcAMP), which is sufficient to induce differentiation in murine F9 stem cells. The induction of UVDRP in F9 and NIH3T3 cells was optimized after 6 and 2 days incubation with RA/dbcAMP respectively. Since NIH3T3 cells were not induced to differentiate by RA/dbcAMP, the upregulation of the UVDRP in mammalian cells would thus seem not to be mediated directly by differentiation. Using a plasmid re-activation assay to estimate DNA repair, we did not find a correlation between DNA repair and UVDRP in RA/dbcAMP-treated cells. The results suggest that UVDRP may have a function other than, or in addition to, its role in DNA repair.

Animals↗
PubMed1996

Molecular cloning, characterization, and sequencing of the hemolysin gene from Edwardsiella tarda.

Hemolysis is a major symptom of diseased eels infected by Edwardsiella tarda. The hemolysin gene of E. tarda strain ET16 was cloned into plasmid pSK and expressed in Escherichia coli. The mol. mass of the functional beta-hemolysin was estimated to be approximately 34 kDa by gel filtration and by SDS-PAGE followed by in situ hemolysin activity analysis. The cloned fragment containing the beta-hemolysin locus from E. tarda strain ET16 expressed in E. coli was estimated to be 5.3 kb in length; the deduced gene product was identical in mol. mass and properties to the extracellular products of E. tarda strain ET16. The presence of EcoRI and XbaI sites within the beta-hemolysin gene of E. tarda was determined from the loss of hemolytic activity in subclones. Analysis of the DNA sequence of a 2,436-bp HaeIII-HindIII fragment that included EcoRI and XbaI sites revealed three ORFs organized as an operon that encoded three predicted polypeptides of 15,874, 7,055, and 34,804 Da. A 34-kDa polypeptide expressing hemolytic activity in cell lysates of the clone DH5 alpha(pETH3E) is very likely the beta-hemolysin encoded by the third ORF. The observation that hemolytic activity appeared in the culture medium of E. tarda, but not in that of E. coli strain DH5 alpha(pETH3E) indicates the existence of a mechanism for transporting the hemolysin across the cell envelope in E. tarda that is different from that of E. coli.

Amino Acid Sequence↗
PubMed1996

Genetic polymorphisms of debrisoquine and S-mephenytoin oxidation metabolism in Chinese populations: a meta-analysis.

Chinese data on the polymorphic metabolism of debrisoquine, metoprolol, codeine and mephenytoin were collected and re-analysed using a meta-analysis method. There were no significant differences in the incidences of poor metabolizer (PM) between the separate series of debrisoquine, metoprolol and codeine, which are the three probe drugs reflecting the same enzyme polymorphism. PMs were detected at low frequencies for debrisoquine (1.20%; 95% confidence interval, CI: 0.67-1.98%), metoprolol (0.72%; CI: 0.29-1.49%) and codeine (0.48%, CI: 0.01-2.68%). The overall estimate of PM was 0.95% (CI: 0.60-1.42%) based on the 2427 determinations of all three probe drugs. The overall mean of PM of mephenytoin was 14.32% (12.26-16.38%) in the 1117 subjects. In summary, the present meta-analysis determined the accurate incidences of the genetic deficiency of S-mephenytoin 4'-hydroxylase (cytochrome P450 2C19) and debrisoquine hydroxylase (cytochrome P450 2D6) in Chinese populations.

China↗