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Fulltext Pharmacogenomics based practice in Malaysia: The attitude, knowledge and adoption by the healthcare professionals

Bannur Z., Bahaman S., Salleh M.Z., Teh L.K.

International Medical Journal Malaysia, 2014;13(1):41-50.

MyJurnal

Introduction: Knowledge, attitude as well as adoption of pharmacogenomics in clinical practice among the pharmacists and physicians in Malaysia have not been reported. This cross-sectional study explores various facets of the two professions as related to pharmacogenomics to determine the need and preferred method to improve education among them. This study also aims to identify the current state of pharmacogenomics practice in Malaysia to help identify barrier and solution to reap advantages from pharmacogenomics practices. Methods: A questionnaire consisting of 38 questions in five parts was adopted and validated. It explores the respondents’ characteristics, attitude, knowledge, adoption and education. It was distributed online to 1500 pharmacists and physicians over five months. Results: Pharmacists differed from the physicians in terms of attitude, knowledge, adoption and education. Overall, adoption rate of pharmacogenomics was found to be low but its anticipation for future adoption is high, and benefits were reported by healthcare professionals who have used the test in a clinical setting. Majority of respondents had poor to fair knowledge and nearly half have had no prior formal teaching on pharmacogenomics. Interest in the education is very high, and most of them preferred to learn pharmacogenomics via continuous professional education programs. Conclusion: Pharmacogenomics is a field that promises many benefits, but to reap these benefits require its implementation in clinical setting. Pharmacists and physicians need to be equipped with adequate knowledge and positive attitude towards pharmacogenomics.

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.

The Implication of the Polymorphisms of COX-1, UGT1A6, and CYP2C9 among Cardiovascular Disease (CVD) Patients Treated with Aspirin

Jalil NJ, Bannur Z, Derahman A, Maskon O, Darinah N, Hamidi H, et al.

J Pharm Pharm Sci, 2015;18(3):474-83.

PMID: 26517138

PURPOSE: Enzymes potentially responsible for the pharmacokinetic variations of aspirin include cyclooxygenase-1 (COX-1), UDP-glucuronosyltransferase (UGT1A6) and P450 (CYP) (CYP2C9). We therefore aimed to determine the types and frequencies of variants of COX-1 (A-842G), UGT1A6 (UGT1A6*2; A541G and UGT1A6*3; A522C) and CYP2C9 (CYP2C9*3; A1075C) in the three major ethnic groups in Malaysia. In addition, the role of these polymorphisms on aspirin-induced gastritis among the patients was investigated.

METHODS: A total of 165 patients with cardiovascular disease who were treated with 75-150 mg daily dose of aspirin and 300 healthy volunteers were recruited. DNA was extracted from the blood samples and genotyped for COX-1 (A-842G), UGT1A6 (UGT1A6*2 and UGT1A6*3) and CYP2C9 (CYP2C9*3; A1075C) using allele specific polymerase chain reaction (AS-PCR).

RESULTS: Variants UGT1A6*2,*3 and CYP2C9*3 were detected in relatively high percentage of 22.83%, 30.0% and 6.50%, respectively; while COX-1 (A-842G) was absent. The genotype frequencies for UGT1A6*2 and *3 were significantly different between Indians and Malays or Chinese. The level of bilirubin among patients with different genotypes of UGT1A6 was significantly different (p-value < 0.05). In addition, CYP2C9*3 was found to be associated with gastritis with an odd ratio of 6.8 (95 % Cl OR: 1.39 - 33.19; P = 0.033).

CONCLUSION: Screening of patients with defective genetic variants of UGT1A6 and CYP2C9*3 helps in identifying patients at risk of aspirin induced gastritis. However, a randomised clinical study of bigger sample size would be needed before it is translated to clinical use.

Fulltext Coupling Genotyping and Computational Modeling in Prediction of Anti-epileptic Drugs that cause Stevens Johnson Syndrome and Toxic Epidermal Necrolysis for Carrier of HLA-B*15:02

Teh LK, Selvaraj M, Bannur Z, Ismail MI, Rafia H, Law WC, et al.

J Pharm Pharm Sci, 2016;19(1):147-60.

PMID: 27096699 DOI: 10.18433/J38G7X

PURPOSE: The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are investigated.

METHODS: DNA was extracted from eighty-six patients. The patients were genotyped by AS-PCR. Computational modeling of the HLA-B*15:02 followed by docking studies were performed to screen 26 AEDs that may induce ADR among HLA-B*15:02 carriers.

RESULTS: Odd ratio for CBZ induced SJS/TEN and HLA-B*15:02 was 609.0 (95% CI: 23-15873; p=0.0002). Molecular modeling studies showed that acetazolamide, ethosuxiamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone and sodium-valproate may induce ADR in HLA-B*15:02 carriers alike CBZ. Conclusion. We confirmed HLA-B*15:02 as a predictor of SJS/TEN and recommend pre-screening. Computational prediction of DIHR is useful in personalized medicine.

Isolating the metabolic pathways involved in the hepatoprotective effect of Muntingia calabura against CCl4-induced liver injury using LC/MS Q-TOF

Rofiee MS, Yusof MI, Abdul Hisam EE, Bannur Z, Zakaria ZA, Somchit MN, et al.

J Ethnopharmacol, 2015 May 26;166:109-18.

PMID: 25792013 DOI: 10.1016/j.jep.2015.03.016

Muntingia calabura L. has been used in Southeast Asia and tropical America as antipyretic, antiseptic, analgesic, antispasmodic and liver tonic. This study aims to determine the acute toxicity and the metabolic pathways involved in the hepatoprotective mechanism of M. calabura.

Fulltext Metabolomics and partial least square discriminant analysis to predict history of myocardial infarction of self-claimed healthy subjects: validity and feasibility for clinical practice

Mohamad N, Ismet RI, Rofiee M, Bannur Z, Hennessy T, Selvaraj M, et al.

J Clin Bioinforma, 2015;5:3.

PMID: 25806102 DOI: 10.1186/s13336-015-0018-4

The dynamics of metabolomics in establishing a prediction model using partial least square discriminant analysis have enabled better disease diagnosis; with emphasis on early detection of diseases. We attempted to translate the metabolomics model to predict the health status of the Orang Asli community whom we have little information. The metabolite expressions of the healthy vs. diseased patients (cardiovascular) were compared. A metabotype model was developed and validated using partial least square discriminant analysis (PLSDA). Cardiovascular risks of the Orang Asli were predicted and confirmed by biochemistry profiles conducted concurrently.

Potential of dihydropyrimidine dehydrogenase genotypes in personalizing 5-fluorouracil therapy among colorectal cancer patients

Teh LK, Hamzah S, Hashim H, Bannur Z, Zakaria ZA, Hasbullani Z, et al.

Ther Drug Monit, 2013 Oct;35(5):624-30.

PMID: 23942539 DOI: 10.1097/FTD.0b013e318290acd2

Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine catabolic enzyme involved in the initial and rate-limiting step of the catabolic pathway of toxic metabolites of 5-fluorouracil (5-FU). Several studies have reported that deficiency of DPD and polymorphisms of its gene are related to 5-FU toxicities and death. Association between serum concentration of 5-FU and its related toxicity has also been previously demonstrated. Hence, this study aims to understand the role of DPYD variants in serum level of 5-FU and the risk of developing toxicity to prevent adverse reactions and maximize therapy outcome for personalized medicine.

Fulltext Increased risks of cardiovascular diseases and insulin resistance among the Orang Asli in Peninsular Malaysia

Tuan Abdul Aziz TA, Teh LK, Md Idris MH, Bannur Z, Ashari LS, Ismail AI, et al.

BMC Public Health, 2016;16(1):284.

PMID: 27009064 DOI: 10.1186/s12889-016-2848-9

Despite the strategic development plan by the authorities for the Orang Asli, there are six subtribes of which their population numbers are small (less than 700). These minorities were not included in most of the health related studies published thus far. A comprehensive physiological and biomedical updates on these small subtribes in comparison to the larger subtribes and the urban Malay population is timely and important to help provide appropriate measures to prevent further reduction in the numbers of the Orang Asli.

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