MyMedR

The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach

Bannur Z, Teh LK, Hennesy T, Rosli WR, Mohamad N, Nasir A, et al.

Clin Biochem, 2014 Apr;47(6):427-31.

PMID: 24582698 DOI: 10.1016/j.clinbiochem.2014.02.013

Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible.

Fulltext Draft Genome Sequence of a Clinical Isolate of Mycobacterium tuberculosis Strain PR05

Ismail A, Teh LK, Ngeow YF, Norazmi MN, Zainul ZF, Tang TH, et al.

Genome Announc, 2013;1(3).

PMID: 23788553 DOI: 10.1128/genomeA.00397-13

We report the annotated genome sequence of a clinical isolate, Mycobacterium tuberculosis strain PR05, which was isolated from the human cerebrospinal fluid of a patient diagnosed with tuberculosis.

The relevance of CYP2D6 genetic polymorphism on chronic metoprolol therapy in cardiovascular patients

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.

CYP2D6 phenotypes among Malays in Malaysia

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.

Genetic polymorphism of CYP2D6 in Chinese subjects in Malaysia

Ismail R, Teh LK, Amir J, Alwi Z, Lopez CG

J Clin Pharm Ther, 2003 Aug;28(4):279-84.

PMID: 12911679

Although Malaysian Chinese share an origin with the mainland Chinese, their evolution has been influenced by intermarriages. With a gene such as CYP2D6, which is highly polymorphic, it is expected that the Malaysian Chinese would exhibit a polymorphism profile different from those of the Chinese populations in other geographical locations.

Chloramphenicol in children: dose, plasma levels and clinical effects

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.

Genetic polymorphism of CYP2D6: Malaysian Indians have the highest frequency for CYP2D6*4 in Asia

Ismail R, Teh LK

Eur J Clin Pharmacol, 2001 Oct;57(8):617-8.

PMID: 11758642

Fulltext The genome sequence of Acinetobacter baumannii isolated from a septicemic patient in a local hospital in Malaysia

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.

An assessment of three noncommercial DNA extraction methods from dried blood spots for beta-thalassaemia mutation identification

Karthipan SN, George E, Jameela S, Lim WF, Teh LK, Lee TY, et al.

Int J Lab Hematol, 2011 Oct;33(5):540-4.

PMID: 21884505 DOI: 10.1111/j.1751-553X.2011.01304.x

Dried blood spots (DBS) are currently the recommended sample collection method for newborn screening programmes in America. Early diagnosis of beta-thalassaemia screening is essential as it provides an added advantage especially in sickle cell disease. Beta-thalassaemia frequency is high in many poor countries, and the cost of using commercial DNA extraction kits can be prohibitive. Our study assessed three methods that use minimal reagents and materials to extract DNA from DBS for beta-thalassaemia identification.

Fulltext Genome sequence of Proteus mirabilis strain PR03, isolated from a local hospital in Malaysia

Khalid MI, Teh LK, Lee LS, Zakaria ZA, Salleh MZ

Genome Announc, 2013;1(3).

PMID: 23792750 DOI: 10.1128/genomeA.00327-13

Proteus mirabilis is one of the pathogenic agents that commonly causes urinary tract infections among elderly individuals and long-term catheterized patients. Here, we report a draft genome sequence of Proteus mirabilis strain PR03 (3,932,623 bp, with a G+C content of 38.6%) isolated from a local hospital in Malaysia.

Fulltext Analysis of α1 and α2 globin genes among patients with hemoglobin Adana in Malaysia

Lee TY, Lai MI, Ismail P, Ramachandran V, Tan JA, Teh LK, et al.

Genet. Mol. Res., 2016 Apr 07;15(2).

PMID: 27173219 DOI: 10.4238/gmr.15027400

Hemoglobin (Hb) Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a non-deletional α-thalassemia variant found in Malaysia. An improvement in the molecular techniques in recent years has made identification of Hb Adana much easier. For this study, a total of 26 Hb Adana α-thalassemia intermedia and 10 Hb Adana trait blood samples were collected from patients. Common deletional and non-deletional α-thalassemia genotypes were determined using multiplex gap polymerase chain reaction (PCR) and multiplex ARMS PCR techniques. Identification of the Hb Adana location on the α-globin gene was carried out using genomic sequencing and the location of the mutation was confirmed via restriction fragment length polymorphism-PCR. Among the 36 samples, 24 (66.7%) had the -α(3.7)/α(Cd59)α mutation, while the -α(3.7)/α(Cd59)α mutation accounted for 2 samples (5.6%) and the remaining 10 (27.8%) samples were α/α(Cd59)α. All 36 samples were found to have the Hb Adana mutation on the α2-globin gene. The position of the α-globin gene mutation found in our cases was similar to that reported in Indonesia (16%) but not to that in Turkey (0.6%). Our results showed that the Hb Adana mutation was preferentially present in the α2-globin genes in Malays compared to the other ethnicities in Malaysia. Thus, the Malays might have similar ancestry based on the similarities in the Hb Adana position.

Rapid detection of α-thalassaemia variants using droplet digital PCR

Lee TY, Lai MI, Ramachandran V, Tan JA, Teh LK, Othman R, et al.

Int J Lab Hematol, 2016 Aug;38(4):435-43.

PMID: 27349818 DOI: 10.1111/ijlh.12520

INTRODUCTION: Alpha thalassaemia is a highly prevalent disease globally and is a well-known public health problem in Malaysia. The deletional forms of the mutation are the most common forms found in alpha thalassaemia. The three most common deletional alpha thalassaemia found in this region include --(SEA) deletion, -α(3.7) rightward and -α(4.2) leftward deletions. The prevalence rate of triplication alpha cases such as ααα(anti3.7) and ααα(anti4.2) is not known in Malaysia although it plays a role in exacerbating the clinical phenotypes in beta thalassaemia carriers. Recently, there have been more reported cases of rare alpha thalassaemia mutations due to the advancement of molecular techniques involved in thalassaemia detections. Therefore, it is essential to develop a new method which allows the detection of different alpha thalassaemia mutations including the rare ones simultaneously and accurately.

METHODS: The purpose of this study was to design an assay for the detection of triplications, common and rare deletional alpha thalassaemia using droplet digital PCR (ddPCR).

RESULTS: This is a quantitative detection method to measure the changes of copy number which can detect deletions, duplications and triplications of the alpha globin gene simultaneously.

CONCLUSION: In conclusion, ddPCR is an alternative method for rapid detection of alpha thalassaemia variants in Malaysia.

Fulltext Genetic variants in HBS1L-MYB with Hb subtypes level among Filipino β°-deletion carriers coinherited with -α3.7 deletion

Lim, L. N., Yu, K. S., Chua, S. M., George, E., Lai, M. I., Wong, L., et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):47-47.

MyJurnal

Introduction: Filipino β°-deletion is predominant among the β-thalassaemia patients in the indigenous population of Sabah, Malaysia particularly among the Kadazandusun. Individuals who co-inherit with α- and β-thalassaemia will demonstrate milder clinical symptoms with modified complete blood count (CBC) and Hb subtype parameters. HBS1L-MYB variants act as one of the key regulator of haematopoiesis and erythropoiesis and display strong association
with variation of HbF levels. Therefore, this study aims to evaluate the association between genetic variants in HBS1L-MYB with Hb subtypes level among Filipino β°-deletion carriers co-inherited with -α3.7 deletion. Methods: Filipino β°-deletion and -α3.7 deletion were identified using gap-polymerase chain reaction (PCR). A total of 34 subjects found with coinheritance of Filipino β°-deletion and -α3.7 deletion were subjected for HBS1L-MYB intergenic polymorphisms (HMIP) analysis. Hb subtypes level were quantified using BioRad Variant II Hb analyser. Genotyping of HBS1L-MYB variants rs9399137 and rs11759553 was done using own designed tetra primer ARMS-PCR. Results: The minor allele frequencies (MAF) of the two HMIP is found more than 0.05 (rs11759553, MAF=0.18 and rs9399137, MAF=0.15), indicating the significance of these variants among the study subjects. Significant difference was found between HbF level and HBS1L-MYB variant rs11759553 with p-value less than 0.05 (p=0.001). Subjects with homozygous genotype for rs11759553 (T/T) was found with higher HbF, followed by heterozygous (A/T) and wild type (A/A). rs11759553 and rs9399137 was found did not influence the level of HbA and HbA2. HMIP of rs11759553 and rs9399137 are found significant among Filipino β°-deletion carriers co-inherited with -α3.7deletion with its high minor allelic frequency and high HbF level. Strong association with HbF level was demonstrated when
coinheritance of rs11759553. Conclusion: This study demonstrates that there are significant associations between certain genetic variants in HBS1L-MYB with Hb subtypes level among Filipino β°-deletion carriers co-inherited with -α3.7 deletion.

Muntingia calabura: a review of its traditional uses, chemical properties, and pharmacological observations

Mahmood ND, Nasir NL, Rofiee MS, Tohid SF, Ching SM, Teh LK, et al.

Pharm Biol, 2014 Dec;52(12):1598-623.

PMID: 25068675 DOI: 10.3109/13880209.2014.908397

Different parts of Muntingia calabura L. (Elaeocarpaceae), or "kerukup siam" in Malay, have been reported to possess medicinal value, supported by a number of scientific studies.

Genetic polymorphism of CYP2C8 in three Malaysian ethnics: CYP2C8*2 and CYP2C8*3 are found in Malaysian Indians

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.

A simple multiplex PCR method for the concurrent detection of three CYP2C8 variants

Muthiah YD, Lee WL, Teh LK, Ong CE, Salleh MZ, Ismail R

Clin Chim Acta, 2004 Nov;349(1-2):191-8.

PMID: 15469873 DOI: 10.1016/j.cccn.2004.06.024

BACKGROUND: Cytochrome P450 (CYP) 2C8 is a principle enzyme responsible for the metabolism of many clinically important drugs as well as endogenous compounds such as arachidonic acid. The enzyme is genetically polymorphic but a simple method is not available to study its genetic polymorphism. We developed and optimized a variant-specific PCR techniques to detect CYP2C8*2, CYP2C8*3 and CYP2C8*4.
METHOD: Genomic DNA was extracted from blood using standard extraction methods. A two-step PCR method was developed to detect simultaneously three CYP2C8 variants. In the first PCR (PCR1), specific regions from exons 3, 5 and 8 of the CYP2C8 gene were amplified. The products were used as templates in parallel alleles-specific PCR (PCR2). This method was tested against DNA samples obtained from 57 healthy Malaysian volunteers.
RESULT: The bands of interest were successfully amplified. This method showed specific and reproducible results when tested on healthy volunteers. DNA sequencing further confirmed genotype results obtained from current method.
CONCLUSION: We have successfully developed and optimized a multiplex PCR method suitable for use in population studies of CYP2C8 polymorphism.

Fulltext Draft Genome Sequence of Streptococcus agalactiae PR06

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.

Role of pharmacodiagnostic of CYP2C9 variants in the optimization of warfarin therapy in Malaysia: a 6-month follow-up study

Ngow H, Teh LK, Langmia IM, Lee WL, Harun R, Ismail R, et al.

Xenobiotica, 2008 Jun;38(6):641-51.

PMID: 18570163 DOI: 10.1080/00498250801999087

1. A retrospective study was conducted to explore the importance of CYP2C9 genotyping for the initiation and maintenance therapy of warfarin in clinical practice. A total of 191 patients on warfarin therapy in a local hospital were recruited after written informed consent. Their medical records were reviewed and no intervention of warfarin dose was performed. 2. A total of 5 ml of blood were taken from each subject for DNA extraction and identification of 1, 2, 3 and 4 CYP2C9 alleles, using a nested-allele-specific-multiplex-polymerase chain reaction (PCR). Half the patients were Malays and the remaining were Chinese. 3. Two genotypes were detected; 93.2% had CYP2C9 1/1 and 6.8% were CYP2C9 1/3. Warfarin doses were higher in patients with CYP2C91/1. Patients with the 1/3 genotype experienced a higher rate of serious and life-threatening bleeding; 15.4 versus 6.2 per 100 patients per 6 months. 4. The observation clearly highlights the inadequacy of the current dosing regimens and the need to move toward a more individualized approach to warfarin therapy. Prospective clinical studies are now being conducted to assess dosing algorithms that incorporate the contribution of the genotype to allow the individualization of warfarin dose.

Fulltext CYP2C9 polymorphism: prevalence in healthy and warfarin-treated Malay and Chinese in Malaysia

Ngow HA, Wan Khairina WM, Teh LK, Lee WL, Harun R, Ismail R, et al.

Singapore Med J, 2009 May;50(5):490-3.

PMID: 19495518

Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different. CYP2C9 has been reported to be the enzyme responsible for the metabolism of many drugs, including warfarin and other drugs with a narrow therapeutic index. Realising the importance of inter-individual differences in the genetic profile in determining the outcome of a drug therapy, this study was conducted to explore the types and frequencies of CYP2C9 alleles in healthy and warfarin-treated Malays and Chinese, the two major ethnic groups in Malaysia. We aimed to evaluate the prevalence of the types and frequencies of common CYP2C9 alleles (*1, *2, *3 and *4) among the healthy unrelated individuals and diseased patients prescribed with warfarin.

Complete mitochondrial genome of Malaysian Mahseer (Tor tambroides)

Norfatimah MY, Teh LK, Salleh MZ, Mat Isa MN, SitiAzizah MN

Gene, 2014 Sep 15;548(2):263-9.

PMID: 25042454 DOI: 10.1016/j.gene.2014.07.044

This is the first documentation of the complete mitochondrial genome sequence of the Malaysian Mahseer, Tor tambroides. The 16,690 bp mitogenome with GenBank accession number JX444718 contains 13 protein genes, 22 tRNAs, two rRNAs, and a noncoding control region (D-loop) as is typical of most vertebrates. The phylogenomic reconstruction of this newly generated data with 21 Cypriniformes GenBank accession ID concurs with the recognized status of T. tambroides within the subfamily Cyprininae. This is in agreement with previous hypotheses based on morphological and partial mitochondrial analyses.

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