Displaying publications 1 - 20 of 33 in total

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  1. Hoh BP, Abdul Rahman T, Yusoff K
    Hereditas, 2019;156:1.
    PMID: 30636949 DOI: 10.1186/s41065-019-0080-1
    Prevalence of hypertension (HTN) varies substantially across different populations. HTN is not only common - affecting at least one third of the world's adult population - but is also the most important driver for cardiovascular diseases. Yet up to a third of hypertensive patients are resistant to therapy, contributed by secondary hypertension but more commonly the hitherto inability to precisely predict response to specific antihypertensive agents. Population and individual genomics information could be useful in guiding the selection and predicting the response to treatment - an approach known as precision medicine. However this cannot be achieved without the knowledge of genetic variations that influence blood pressure (BP). A number of evolutionary factors including population demographics and forces of natural selection may be involved. This article explores some ideas on how natural selection influences BP regulation in ethnically and geographically diverse populations that could lead to them being susceptible to HTN. We explore how such evolutionary factors could impact the implementation of precision medicine in HTN. Finally, in order to ensure the success of precision medicine in HTN, we call for more initiatives to understand the genetic architecture within and between diverse populations with ancestry from different parts of the world, and to precisely classify the intermediate phenotypes of HTN.
  2. Awuah WA, Tenkorang PO, Ng JC, Abdul-Rahman T
    Neurosurgery, 2023 Jul 01;93(1):e16.
    PMID: 37097024 DOI: 10.1227/neu.0000000000002515
  3. Sahlan N, Fadzilah MN, Muslim A, Shaari SA, Abdul Rahman T, Hoh BP
    Med J Malaysia, 2019 08;74(4):320-325.
    PMID: 31424040
    INTRODUCTION: Prevalence of Hepatitis B virus (HBV) infection among the non-indigenous people in Malaysia has been well established and range between 3% and 5%. However, data from the indigenous (Orang Asli) people is still lacking. The Negrito population is the most remotely located Orang Asli tribe with limited access to health care facilities. This study was undertaken to determine the epidemiology and seroprevalence of HBV infection among the Negrito.

    METHODS: Surveys were conducted in five Negrito settlements in Kelantan and Perak states in Malaysia. A total of 150 participants were recruited. Clinical history was taken and physical examination was performed. Five millilitres of whole blood were collected and tested for hepatitis B surface antigen (HBsAg) using electrochemiluminescence immunoassay.

    RESULTS: Participants were mainly from the Bateq (49.3%) and Mendriq (29.4%) sub-tribes. Overall, 13 subjects (8.7 %); nine males and four females were HBsAg positive. Nine of the HBsAg positive subjects were ≥35 years old. All of them had history of home deliver without evidence of antenatal record. Six (46%) of the HBsAg positive subjects had tattoo and body piercing in the past.

    CONCLUSION: The prevalence of HBV infection rate amongst the Negrito tribe is almost three-fold compared to the national rates. The reason for this finding remains unclear. Tattooing, body piercing and vertical transmission could be the main possible routes of transmission of HBV among the Negrito population in Malaysia.

  4. Muid S, Abu Bakar NA, Abdul Rahman T, Tengku Ismail TS, Kholin SF, Suvorov AV, et al.
    Malays J Pathol, 2019 Dec;41(3):283-292.
    PMID: 31901913
    INTRODUCTION: Apart from inflammation and endothelial dysfunction, other key components in the development of atherogenesis include prothrombogenesis and oxidative stress. The effects of long-term confinement and isolation, exposure to radiation and different gravity forces during space travel could potentially increase the long-term risk of atherosclerosis. To the best of our knowledge, this is the first study determining the status of prothrombogenesis and oxidative stress in six cosmonauts subjected to the longest duration of confined isolation period of 520 days in preparation for prospective undetermined manned space travel to Mars.

    MATERIALS AND METHODS: This collaborative research between the National Space Agency (ANGKASA), Universiti Teknologi MARA, Malaysia and Institute of Biomedical Problems (IBMP), Russia was conducted at the Russian Academy of Sciences IBMP, Moscow, Russia. Six multi-national cosmonauts were assigned to live in a ground-based confined module for 520 days. Standard exercise and diet regime were instituted throughout the isolation phase. Six age, ethnic and gender-matched healthy, free-living ground controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of prothrombogenesis [plasminogen activator inhibitor-1 (PAI-1) and homocysteine] and oxidative stress [oxidised low-density lipoprotein (ox-LDL) and malondialdehyde (MDA)].

    RESULTS: There were significantly lower concentrations of PAI-1 and homocysteine in cosmonauts during confinement compared to the controls. There were no significant differences seen in the concentrations of biomarkers of oxidative stress during confinement but there was a significant percentage change increment for serum MDA in cosmonauts.

    CONCLUSION: Long-term confinement decreased the risk of prothrombogenesis and this could be attributed to the exercise and diet regime which includes omega-3 fatty acids supplementation given to the crew members during their confinement period. However, oxidative damage could not be excluded and may be attributed to the influence of psychological stress during this prolonged confinement.

  5. Adebusoye FT, Awuah WA, Swaminathan N, Ghosh S, Wellington J, Abdul-Rahman T, et al.
    Neurosurgery, 2023 Aug 01;93(2):e30-e31.
    PMID: 37192472 DOI: 10.1227/neu.0000000000002527
  6. Tenkorang PO, Awuah WA, Ng JC, Kalmanovich J, Nazir A, Yarlagadda R, et al.
    Neurosurgery, 2023 Mar 01;92(3):e72-e73.
    PMID: 36700753 DOI: 10.1227/neu.0000000000002330
  7. Wireko AA, Ng JC, David L, Abdul-Rahman T, Sikora V, Isik A
    Int J Surg, 2023 Apr 10;110(1):571-3.
    PMID: 37026787 DOI: 10.1097/JS9.0000000000000000
  8. Mokhsin A, Mokhtar SS, Mohd Ismail A, M Nor F, Shaari SA, Nawawi H, et al.
    BMJ Open, 2018 12 04;8(12):e021580.
    PMID: 30518581 DOI: 10.1136/bmjopen-2018-021580
    OBJECTIVES: To determine the prevalence of metabolic syndrome (MS), ascertain the status of coronary risk biomarkers and establish the independent predictors of these biomarkers among the Negritos.

    SETTINGS: Health screening programme conducted in three inland settlements in the east coast of Malaysia and Peninsular Malaysia.

    SUBJECTS: 150 Negritos who were still living in three inland settlements in the east coast of Malaysia and 1227 Malays in Peninsular Malaysia. These subjects were then categorised into MS and non-MS groups based on the International Diabetes Federation (IDF) consensus worldwide definition of MS and were recruited between 2010 and 2015. The subjects were randomly selected and on a voluntary basis.

    PRIMARY AND SECONDARY OUTCOME MEASURES: This study was a cross-sectional study. Serum samples were collected for analysis of inflammatory (hsCRP), endothelial activation (sICAM-1) and prothrombogenesis [lp(a)] biomarkers.

    RESULTS: MS was significantly higher among the Malays compared with Negritos (27.7%vs12.0%). Among the Malays, MS subjects had higher hsCRP (p=0.01) and sICAM-1 (p<0.05) than their non-MS counterpart. There were no significant differences in all the biomarkers between MS and the non-MS Negritos. However, when compared between ethnicity, all biomarkers were higher in Negritos compared with Malays (p<0.001). Binary logistic regression analysis affirmed that Negritos were an independent predictor for Lp(a) concentration (p<0.001).

    CONCLUSIONS: This study suggests that there may possibly be a genetic influence other than lifestyle, which could explain the lack of difference in biomarkers concentration between MS and non-MS Negritos and for Negritos predicting Lp(a).

  9. Mehta A, Cheng Ng J, Andrew Awuah W, Huang H, Kalmanovich J, Agrawal A, et al.
    Ann Med Surg (Lond), 2022 Dec;84:104803.
    PMID: 36582867 DOI: 10.1016/j.amsu.2022.104803
    Robotic surgery has applications in many medical specialties, including urology, general surgery, and surgical oncology. In the context of a widespread resource and personnel shortage in Low- and Middle-Income Countries (LMICs), the use of robotics in surgery may help to reduce physician burnout, surgical site infections, and hospital stays. However, a lack of haptic feedback and potential socioeconomic factors such as high implementation costs and a lack of trained personnel may limit its accessibility and application. Specific improvements focused on improved financial and technical support to LMICs can help improve access and have the potential to transform the surgical experience for both surgeons and patients in LMICs. This review focuses on the evolution of robotic surgery, with an emphasis on challenges and recommendations to facilitate wider implementation and improved patient outcomes.
  10. Wireko AA, Ohenewaa Tenkorang P, Fosuah Debrah A, Akin-Olugbemi T, Yarlagadda R, Mehta A, et al.
    Int J Surg, 2023 Mar 01;109(3):534-535.
    PMID: 36928287 DOI: 10.1097/JS9.0000000000000011
  11. Wireko AA, Tenkorang PO, Ng JC, David L, Yarlagadda R, Abdul-Rahman T, et al.
    Int J Surg, 2023 Jun 01;109(6):1808-1809.
    PMID: 36927817 DOI: 10.1097/JS9.0000000000000048
  12. Awuah WA, Ng JC, Nazir A, Tenkorang PO, Yarlagadda R, Kalmanovich J, et al.
    Int J Surg, 2023 May 01;109(5):1080-1082.
    PMID: 36927691 DOI: 10.1097/JS9.0000000000000125
  13. Awuah WA, Tenkorang PO, Adebusoye FT, Ng JC, Wellington J, Abdul-Rahman T, et al.
    Postgrad Med J, 2023 Dec 21;100(1179):1-3.
    PMID: 37857514 DOI: 10.1093/postmj/qgad100
  14. Mohamad N, Ismet RI, Rofiee M, Bannur Z, Hennessy T, Selvaraj M, et al.
    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.
  15. Ang GY, Yu CY, Johari James R, Ahmad A, Abdul Rahman T, Mohd Nor F, et al.
    Ann Hum Biol, 2018 Mar;45(2):166-169.
    PMID: 29447003 DOI: 10.1080/03014460.2018.1440004
    BACKGROUND: CYP3A5 is the predominant sub-family of biotransformation enzymes in the liver and the genetic variations in CYP3A5 are an important determinant of inter-individual and inter-ethnic differences in CYP3A-mediated drug disposition and response.

    AIM: This study aims to investigate the genetic polymorphisms of CYP3A5 among the Orang Asli in Peninsular Malaysia using a next generation sequencing platform.

    METHODS: Genomic DNAs were extracted from blood samples of the three main Orang Asli tribes and whole-genome sequencing was performed.

    RESULTS: A total of 61 single nucleotide polymorphisms were identified and all the SNPs were located in introns except rs15524, which is in the 3'UTR, and 11 of these polymorphisms were novel. Two allelic variants and three genotypes were identified in the Orang Asli. The major allelic variant was the non-functional CYP3A5*3 (66.4%). The percentages of Orang Asli with CYP3A5*3/*3 (47.2%) and CYP3A5*1/*3 (38.1%) genotypes are more than twice the percentage of Orang Asli with CYP3A5*1/*1 (14.8%) genotype. Almost half of the Orang Asli harboured CYP3A5 non-expressor genotype (CYP3A5*3/*3).

    CONCLUSIONS: The predominance of the CYP3A5 non-expressor genotype among the Orang Asli was unravelled and the findings in this study may serve as a guide for the optimisation of pharmacotherapy for the Orang Asli community.

  16. Yu CY, Ang GY, Subramaniam V, Johari James R, Ahmad A, Abdul Rahman T, et al.
    Genet Test Mol Biomarkers, 2017 Jul;21(7):409-415.
    PMID: 28525288 DOI: 10.1089/gtmb.2016.0235
    AIMS: CYP2D6 is one of the major enzymes in the cytochrome P450 monooxygenase system. It metabolizes ∼25% of prescribed drugs and hence, the genetic diversity of a CYP2D6 gene has continued to be of great interest to the medical and pharmaceutical industries. This study was designed to perform a systematic analysis of the CYP2D6 gene in six subtribes of the Malaysian Orang Asli.

    METHODS: Genomic DNAs were extracted from the blood samples followed by whole-genome sequencing. The reads were aligned to the reference human genome hg19 and variants in the CYP2D6 gene were analyzed. CYP2D6*5 and duplication of CYP2D6 were analyzed using previously established methods.

    RESULTS: A total of 72 single nucleotide polymorphisms were identified. CYP2D6*1, *2, *4, *5, *10,*41, and duplication of the gene were found in the Orang Asli, whereby CYP2D6*2 and *41 alleles are reported for the first time in the Malaysian population.

    CONCLUSION: The findings in this study provide insights into the genetic polymorphisms of CYP2D6 in the Orang Asli of Peninsular Malaysia.

  17. Awuah WA, Kalmanovich J, Mehta A, Huang H, Abdul-Rahman T, Cheng Ng J, et al.
    Curr Top Med Chem, 2023;23(5):389-402.
    PMID: 36593538 DOI: 10.2174/1568026623666230102095836
    Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mortality rate. Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable. Various methods, such as drug repositioning, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later. These medications have a high affinity for serotonin receptors such as 5- HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.
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