Displaying publications 1 - 20 of 107 in total

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  1. Teh LK, Bertilsson L
    Drug Metab. Pharmacokinet., 2012;27(1):55-67.
    PMID: 22185816
    CYP2D6 has received intense attention since the beginning of the pharmacogenetic era in the 1970s. This is because of its involvement in the metabolism of more than 25% of the marketed drugs, the large geographical and inter-ethnic differences in the genetic polymorphism and possible drug-induced toxicity. Many interesting reviews have been published on CYP2D6 and this review aims to reinstate the importance of the genetic polymorphism of CYP2D6 in different populations as well as some clinical implications and important drug interactions.
  2. Ismail R, Teh LK
    J Clin Pharm Ther, 2006 Feb;31(1):99-109.
    PMID: 16476126
    CYP2D6 polymorphisms are well described in normal populations but there are few data on its clinical significance. We therefore investigated the influence of CYP2D6 polymorphism on steady-state plasma concentrations and apparent oral clearance of metoprolol in patients with cardiovascular diseases.
  3. Teh LK, Lim LF, Lim LN, Teh YL, George E, Lee TY
    MyJurnal
    Alpha thalassaemia is one of the haemoglobin disordersin which the carriers of alpha thalassaemia may have normal haemoglobin level and are eligible to donate blood which may bring complications. This study is to investigate the interaction of haematological parameter with α-globin genotypes among eligible blood donors. Materials & Methods: A cohort study with 270 eligible blood donors were analysed for red cell indices. Alpha-globin (α-globin) genotyping was performed for seven deletions, six point mutations and two triplications. Statistical analyses were performed to compare the α-globin genotypes with haematological data. Results: High prevalence of α-thalassaemia carriers (7.7%, 21/270) was found among blood donors. All of them did not show anaemic pictures with a normal Hb level (>12 gm/dl). Five genotypes were identified consisting of 249 αα/αα (92.2%), nine -α3.7/αα (3.3%), nine--SEA/αα (3.3%), two -α4.2/αα (0.7%) and one ααCS/αα (0.4%). Different α-globin genotypes showed a significant difference in RBC, MCV, MCH, MCHC, RDW, and Hct/Hb ratio (p
  4. Sivadas A, Salleh MZ, Teh LK, Scaria V
    Pharmacogenomics J, 2017 10;17(5):461-470.
    PMID: 27241059 DOI: 10.1038/tpj.2016.39
    Expanding the scope of pharmacogenomic research by including multiple global populations is integral to building robust evidence for its clinical translation. Deep whole-genome sequencing of diverse ethnic populations provides a unique opportunity to study rare and common pharmacogenomic markers that often vary in frequency across populations. In this study, we aim to build a diverse map of pharmacogenetic variants in South East Asian (SEA) Malay population using deep whole-genome sequences of 100 healthy SEA Malay individuals. We investigated the allelic diversity of potentially deleterious pharmacogenomic variants in SEA Malay population. Our analysis revealed 227 common and 466 rare potentially functional single nucleotide variants (SNVs) in 437 pharmacogenomic genes involved in drug metabolism, transport and target genes, including 74 novel variants. This study has created one of the most comprehensive maps of pharmacogenetic markers in any population from whole genomes and will hugely benefit pharmacogenomic investigations and drug dosage recommendations in SEA Malays.
  5. Izwan I, Teh LK, Salleh MZ
    Genom Data, 2015 Dec;6:128-9.
    PMID: 26697353 DOI: 10.1016/j.gdata.2015.08.028
    Acinetobacter baumannii is a Gram negative, strictly aerobic clinical pathogen causing mostly nosocomial infections globally. The DNA of an isolate from the blood of a local septicemic patient was sequenced using the Illumina GA IIx. The draft genome generated is 4,178,008 bp with a G + C content of 42%. From the annotation results, 47 resistance determinants including 16 multidrug resistance (MDR) genes were identified. The data may be accessed via the GenBank WGS master accession number APWV00000000.
  6. Lee L, Teh L, Zainuddin Z, Salleh M
    Stand Genomic Sci, 2014 Jun 15;9(3):933-9.
    PMID: 25197474 DOI: 10.4056/sigs.3887716
    We report the genome sequence of a healthcare-associated MRSA type ST239 clone isolated from a patient with septicemia in Malaysia. This clone typifies the characteristics of ST239 lineage, including resistance to multiple antibiotics and antiseptics.
  7. Mz IS, Teh LK, Salleh MZ
    Genome Announc, 2013;1(3).
    PMID: 23766409 DOI: 10.1128/genomeA.00351-13
    Streptococcus agalactiae (group B streptococcus [GBS]) is a Gram-positive bacterium that was first recognized as a causative agent of bovine mastitis. S. agalactiae has subsequently emerged as a significant cause of human diseases. Here, we report the draft genome sequence of S. agalactiae PR06, which was isolated from a septicemic patient in a local hospital in Malaysia.
  8. Zainuddin Z, Teh LK, Suhaimi AW, Ismail R
    J Clin Pharm Ther, 2006 Apr;31(2):187-91.
    PMID: 16635054
    CYP2C9 is one of the major drug metabolizing enzymes for many drugs including warfarin, NSAIDs and losartan. It is polymorphic in many populations. Data on the distribution of CYP2C9 and the implication of CYP2C9 polymorphism in the Malaysian population is lacking. Our objectives were therefore to investigate the prevalence of CYP2C9 variants among unrelated healthy volunteers of Malays, Chinese and Indians in Malaysia.
  9. Ismail R, Hussein A, Teh LK, Nizam Isa M
    J Clin Pharm Ther, 2000 Oct;25(5):379-83.
    PMID: 11123490
    Although they originated from China, Malays have undergone a lot of intermarriages. A study suggested that CYP2D6 poor metabolism (PM) phenotype was more common in Malays compared to Chinese. CYP2D6 is highly polymorphic and is involved in the metabolism of many drugs and has been implicated in some environmentally-induced diseases. It is therefore useful to further study this polymorphism in Malays.
  10. Ong CE, Teh LK, Ismail R
    Med J Malaysia, 2002 Jun;57(2):251-60.
    PMID: 24326665
    Drug interactions can cause iatrogenic disease. If concurrent medications are taken, the potential exists for a drug interaction to occur. Renewed interest in the topic interactions has been generated by the fatal interactions involving non-sedating histamine H-1 antagonists and the recent intriduction of two therapeutic agents, the selective serotonin reuptake inhibitors (SSRIs) and HIV protease inhibitors, for the treatment of depression and AIDS, respectively. These three therapeutic agents have been implicated in clinically significant drug interactions. The consequences of these interactions vary in clinical significance, extent, and effect. Some interactions are theoretical whereas others may lead to severe iatrogenic adverse experiences including lethal consequences.The purpose of this review is to alert the medical practioner to potential drug interactions that may occur when these drugs are prescribed to patients. The pharmacological basis and clinical signficance of these interactions are reviewed. The pharmacological mechanisms underlying these interactions are illustrative of those that may be involved for many other medications. Doctors should be aware of the potential pitfall that may occur when certain groups of drugs are prescribed with concurrent medications.
  11. Ismail R, Teh LK, Choo EK
    Ann Trop Paediatr, 1998 Jun;18(2):123-8.
    PMID: 9924573
    Despite concerns about adverse effects, chloramphenicol (CMC) continues to be used in certain situations and, due to its low therapeutic index and variable pharmacokinetics, therapeutic drug monitoring (TDM) is often recommended. At our centre, CMC finds applications in typhoid and meningitis and TDM is routinely performed. Elsewhere in Malaysia, however, CMC is used without TDM. We therefore decided to evaluate our TDM for CMC in relation to its roles in CMC therapy in children, who constitute most of our patients. Our objective was also to develop strategies to improve our TDM for CMC use. Data were collected from 168 children given CMC for various indications and monitored by the TDM service. Plasma CMC was determined by HPLC and used to adjust doses to maintain concentrations within a range of 10-25 micrograms/ml. Outcomes measured included daily temperatures and haematological indices. Daily doses and plasma CMC varied greatly. Doses averaged 40.5 mg/kg for neonates and 75.5 for older children. Average peak concentrations were therapeutic in 60% and trough in 42%. Average duration of fever was 6.3 days and it was unaffected by plasma CMC. Typhoid was eradicated in 97% but nine children with other diagnoses died. Side-effects were confined to mild reversible haematological abnormalities which developed in 11% of children at plasma concentrations which tended to be high. We conclude that CMC remains useful in children with typhoid. Its use for other indications, however, should be reviewed. Routine TDM for CMC is probably not warranted, at least until a clearer role is defined by well designed prospective studies.
  12. Choo YX, Teh LK, Tan CX
    Molecules, 2022 Dec 30;28(1).
    PMID: 36615507 DOI: 10.3390/molecules28010313
    Sonication is recognized as a potential food processing method to improve the functional properties of fruit juice. This study evaluated the effects of different sonication durations (20, 40, and 60 min) and thermal pasteurization on the nutritional, antioxidant, and microbial properties of noni juice. Fresh noni juice served as the control. The main organic acids detected were malic (57.54−89.31 mg/100 mL) and ascorbic (17.15−31.55 mg/100 mL) acids. Compared with the fresh sample, the concentrations of these compounds were significantly improved (p < 0.05) in the 60 min sonicated sample but reduced (p < 0.05) in the pasteurized sample. Moreover, sonication for 60 min resulted in increments of scopoletin, rutin, and vanillic acid compared to the fresh sample. The antioxidant activity of the juice sample was improved in the sample sonicated for 60 min. Irrespective of juice processing method, the level of microbial counts in noni juice was within the satisfactory level over the 8 weeks of refrigerated (4 °C) storage. This study highlights the feasibility of using ultrasound processing to enhance the quality of noni juice on the industrial scale.
  13. Zahari Z, Teh LK, Ismail R, Razali SM
    Psychiatr Genet, 2011 Aug;21(4):183-9.
    PMID: 21206399 DOI: 10.1097/YPG.0b013e3283437250
    Variations in the gene for dopamine D2 receptor (DRD2) might have an influence on the outcome of antipsychotic treatment in schizophrenia. The objective of this study was to investigate the influence of DRD2 polymorphisms on treatment outcomes in patients with schizophrenia.
  14. Teh LK, Zahri MK, Zakaria ZA, Ismail R, Salleh MZ
    J Clin Pharm Ther, 2010 Dec;35(6):723-8.
    PMID: 21054465 DOI: 10.1111/j.1365-2710.2009.01146.x
    CYP2C8 is involved in the cytochrome P450 (CYP) epoxygenase pathway. Arachidonic acid metabolites such as epoxyeicosatrienenoic acids and hydroxyeicosatetrenoic acids, produced may have a role in hypertension. We aimed to develop a medium through-put method for screening samples of known and new mutations of CYP2C8 using denaturing high performance liquid chromatography (DHPLC).
  15. Teh LK, Lee WL, Amir J, Salleh MZ, Ismail R
    J Clin Pharm Ther, 2007 Jun;32(3):313-9.
    PMID: 17489883
    P-glycoprotein (PgP) is the most extensively studied ATP-binding cassette (ABC) coded by MDR1 gene. To date, 29 single nucleotide polymorphisms (SNPs) have been identified; but only SNP C3435T has been correlated with intestinal PgP expression levels and shown to influence the absorption of orally taken drugs that are PgP substrates. Individuals homozygous for the T allele have more than fourfold lower PgP expression compared with C/C individuals. We developed a one step primer based allele specific PCR method to detect SNP at C3435T to investigate the distribution of this genotype in the local population.
  16. Nurfadhlina M, Foong K, Teh LK, Tan SC, Mohd Zaki S, Ismail R
    Xenobiotica, 2006 Aug;36(8):684-92.
    PMID: 16891249
    The genetically polymorphic cytochrome P450 (CYP) 2A6 is the major nicotine-oxidase in humans that may contribute to nicotine dependence and cancer susceptibility. The authors investigated the types and frequencies of CYP2A6 alleles in the three major ethnic groups in Malaysia and CYP2A6*1A, CYP2A6*1B, CYP2A6*1x2, CYP2A6*2, CYP2A6*3, CYP2A6*4, CYP2A6*5, CYP2A6*7, CYP2A6*8 and CYP2A6*10 were determined by allele-specific polymerase chain reaction (PCR) in 270 Malays, 172 Chinese and 174 Indians. Except for CYP2A6*2 and *3 that were not detected in the Malays and Chinese, all the other alleles were detected. Frequencies for the CYP2A6*4 allele were 7, 5 and 2%, respectively, in Malays, Chinese and Indians. A statistically significant high frequency of the duplicated CYP2A6*1x2 allele occurred among Chinese. Among Malays and Chinese, the most common allele was CYP2A6*1B, but it was CYP2A6*1A among Indians. These ethnic difference in frequencies suggested that further studies are required to investigate the implications on diseases such as cancer and smoking behaviour among these major ethnic groups in Malaysia.
  17. Teh LK, Zilfalil BA, Marina I, Rosemi BS, Ismail R
    J Clin Pharm Ther, 2004 Dec;29(6):559-64.
    PMID: 15584944 DOI: 10.1111/j.1365-2710.2004.00600.x
    BACKGROUND: Cardiovascular diseases are complex diseases that are influenced by both environmental and genetic factors. CYP2D6 found in the brain and the heart is involved in the metabolism of many environmental and some endogenous substances and neurotransmitters responsible for maintaining homeostasis. This raises an interesting hypothesis that it may have a role in the development of or protection against cardiovascular diseases.
    OBJECTIVE: To study the distribution of genotypes of CYP2D6 among patients with cardiovascular diseases in Malaysia.
    METHOD:We obtained DNA from 128 patients who were followed up for cardiovascular diseases. Polymerase chain reaction-based methods were used to determine common CYP2D6 alleles.
    RESULTS: One hundred and twenty-eight patients were enrolled. Most of the patients also had concurrent illnesses. Eleven genotypes were identified in the patients and 41% carried CYP2D6*1/*10. The second most common genotype was homozygous for the wild type gene, followed by homozygous CYP2D6*10/*10 at 14.48 %. A small percentage of the patients were heterozygous CYP2D6*1/*4. One patient was genotyped homozygous CYP2D6*4/*4 predicting a poor metabolizer prevalence of 0.78% (95% CI +/- 1.52%). Analysis using Hardy-Weinberg equilibrium showed that all of the gnotypes were consistent with equilibrium except for CYP2D6*1/*10 (chi(2); P < 0.05).
    CONCLUSION: Our study suggests a possible involvement of CYP2D6 genotypes in cardiovascular system diseases, which need to be validated by further studies.
  18. Muthiah YD, Lee WL, Teh LK, Ong CE, Ismail R
    J Clin Pharm Ther, 2005 Oct;30(5):487-90.
    PMID: 16164496
    CYP2C8 is genetically polymorphic. Four variants, CYP2C8*2, CYP2C8*3, CYP2C8*4 and CYP2C8*5, which contain mutations in the coding regions have been reported to exhibit different enzyme activity as compared with CYP2C8*1.
  19. Teh LK, Ismail R, Yusoff R, Hussein A, Isa MN, Rahman AR
    J Clin Pharm Ther, 2001 Jun;26(3):205-11.
    PMID: 11422605
    Although Malays shared an origin with Chinese, their evolution saw substantial divergences. Phenotyping studies suggested that they differed in CYP2D6 polymorphism, with higher PM prevalence but lesser right-shift for debrisoquine MRs.
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