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  1. Subramaniam V, Wasiuzzaman S
    Heliyon, 2019 Oct;5(10):e02664.
    PMID: 31687507 DOI: 10.1016/j.heliyon.2019.e02664
    The relationship between geographical diversification (GDI) and profitability (ROA) has yielded mixed findings across various developed countries. This study re-examined the relationship using data of public firms listed on the main market of Bursa Malaysia for the period of 2010-2014 using quantile regression approach. The firms are categorised into small firms and large firms based on the firm size median value. The empirical results show that GDI affects ROA heterogeneously in various quantile levels of the ROA for all firms, small firms and large firms. GDI significantly (positive relationship) influences ROA in the middle quantile region (from quantile 0.25 to 0.75) for all firms, in the low quantile region (from quantile 0.1 to 0.5) for the sample of small firms and in the high quantile region (from quantile 0.5 to 0.9) for the sample of large firms. Therefore, GDI activities could benefit firms, provided that the activities are conducted wisely by taking into account the profitability levels of firms as well as the size of firms. This study contributes to literature on geographical diversification by providing empirical support in the context of an emerging market.
  2. Ng YH, Subramaniam V, Lau YL
    Vet Parasitol, 2015 Nov 30;214(1-2):200-3.
    PMID: 26455572 DOI: 10.1016/j.vetpar.2015.09.032
    Sarcocystosis in meat-producing animals is a major cause of reduced productivity in many countries, especially those that rely on agriculture. Although several diagnostic methods are available to detect sarcocystosis, many are too time-consuming for routine use in abattoirs and meat inspection centers, where large numbers of samples need to be tested. This study aimed to compare the sensitivity of the methylene blue tissue preparation, unstained tissue preparation and nested PCR in the detection of sarcocysts in tissue samples. Approximately three-fold more sarcocysts were detected in methylene blue-stained tissue compared to unstained controls (McNemar's test: P<0.01). Test sensitivity was comparable to that of the gold standard for sarcocyst detection, nested polymerase chain reaction. These results suggest that methylene blue can be used in tissue compression as a rapid, safe, and inexpensive technique for the detection of ruminant sarcocystosis in abattoirs.
  3. Subramaniam V, Stewart MW, Smith JF
    J Pain Symptom Manage, 1999 May;17(5):376-83.
    PMID: 10355217
    To study the process of establishment, and evaluate the outcome of participation, in a self-help support group for people with chronic nonmalignant pain, members of a newly-established, consumer-led group participated in two interviews 5 months apart and a researcher observed group meetings. Participants reported significant benefits from participating in the group. They had a significant increase in functional ability and activity, and reported decreased recourse to health professionals, particularly family physicians. This study indicates that pain support groups can play a valuable role for people in pain, assisting with support and rehabilitation, and meeting needs that health professionals are often not appropriate or able to provide.
  4. Linus-Lojikip S, Subramaniam V, Lim WY, Hss AS
    Complement Ther Clin Pract, 2019 Sep 06;37:73-85.
    PMID: 31521007 DOI: 10.1016/j.ctcp.2019.09.001
    BACKGROUND: This case series describes the survival outcomes of patients who underwent integrative medicine (IM) protocol for ovarian cancer, a treatment protocol, that integrated a carefully selected set of complementary and alternative medicine (CAM) into the conventional treatment for ovarian cancers.

    MATERIALS AND METHODS: Retrospective review of patients' medical records was conducted at a private medical centre that delivered the IM protocol for patients with advanced and recurrent ovarian cancers. We explored and analysed the overall survival and disease progressions of those who received the IM treatment for at least 2 months.

    RESULTS: Forty patients with advanced ovarian cancers fulfilled the inclusion criteria for this case series. An overall of 75% of the cases achieved remission with initial IM treatment, 17.5% had a partial response and 7.5% showed progressive disease. The overall 5-year survival for all 40 cases is 53.1%. When explored further, the 5-year survival for cases who received CAM only is 75%, and cases who received combined limited chemotherapy with CAM had a 5-year survival of 55%. At study endpoint, 11 cases died due to ovarian cancer.

    CONCLUSION: These findings suggest that CAM may be a valuable addition to conventional therapy to treat and improve the survival of patients with ovarian cancers. A formal randomized control trial is required to evaluate the efficacy and long-term outcomes of using IM to treat advanced and recurrent ovarian cancers.

  5. Subramaniam V, Adenan MI, Ahmad AR, Sahdan R
    Malays J Nutr, 2003 Mar;9(1):41-51.
    PMID: 22692531 MyJurnal
    The antioxidant activity of two edible medicinal plants commonly used in Malaysian traditional medicine i.e. Piper sarmentosum (kadok) and Morinda elliptica (mengkudu) were tested for antioxidant activity. The methanolic leave extracts of kadok and mengkudu, at 250ug/ml, were tested using the Xanthine/Xanthine Oxidase (X/XOD) Superoxide Scavenging assay. Both extracts showed high superoxide scavenging assay, 88% and 80% respectively compared to superoxide dismutase (SOD) standard. The crude extracts were further fractionated using column chromatography and tested for superoxide scavenging activity, to obtain antioxidant active fractions. Two active fractions were obtained from kadok, PsFr6-71.3%, PsFr7-71.3%, and one active fraction from mengkudu, MeFr3-86.6%. These active fractions were compared against 14 phenolic compound standards. After a series of HPLC analysis of samples and standards, a natural antioxidant compound was identified in kadok and mengkudu i.e. Naringenin (4',5,7-Trihydroxyflavanone) with 75.7% superoxide scavenging activity. Naringenin is a highly potent natural antioxidant that has been reported in the raw materials of larch and grapefruit extracts. Thus, kadok and mengkudu which contain Naringenin, could be used as antioxidant dietary supplements.
  6. Liew A, Lee CC, Subramaniam V, Lan BL, Tan M
    J Magn Reson Imaging, 2023 Jun;57(6):1728-1740.
    PMID: 36208095 DOI: 10.1002/jmri.28456
    BACKGROUND: Research suggests that treatment of multiple brain metastases (BMs) with stereotactic radiosurgery shows improvement when metastases are detected early, providing a case for BM detection capabilities on small lesions.

    PURPOSE: To demonstrate automatic detection of BM on three MRI datasets using a deep learning-based approach. To improve the performance of the network is iteratively co-trained with datasets from different domains. A systematic approach is proposed to prevent catastrophic forgetting during co-training.

    STUDY TYPE: Retrospective.

    POPULATION: A total of 156 patients (105 ground truth and 51 pseudo labels) with 1502 BM (BrainMetShare); 121 patients with 722 BM (local); 400 patients with 447 primary gliomas (BrATS). Training/pseudo labels/validation data were distributed 84/51/21 (BrainMetShare). Training/validation data were split: 121/23 (local) and 375/25 (BrATS).

    FIELD STRENGTH/SEQUENCE: A 5 T and 3 T/T1 spin-echo postcontrast (T1-gradient echo) (BrainMetShare), 3 T/T1 magnetization prepared rapid acquisition gradient echo postcontrast (T1-MPRAGE) (local), 0.5 T, 1 T, and 1.16 T/T1-weighted-fluid-attenuated inversion recovery (T1-FLAIR) (BrATS).

    ASSESSMENT: The ground truth was manually segmented by two (BrainMetShare) and four (BrATS) radiologists and manually annotated by one (local) radiologist. Confidence and volume based domain adaptation (CAVEAT) method of co-training the three datasets on a 3D nonlocal convolutional neural network (CNN) architecture was implemented to detect BM.

    STATISTICAL TESTS: The performance was evaluated using sensitivity and false positive rates per patient (FP/patient) and free receiver operating characteristic (FROC) analysis at seven predefined (1/8, 1/4, 1/2, 1, 2, 4, and 8) FPs per scan.

    RESULTS: The sensitivity and FP/patient from a held-out set registered 0.811 at 2.952 FP/patient (BrainMetShare), 0.74 at 3.130 (local), and 0.723 at 2.240 (BrATS) using the CAVEAT approach with lesions as small as 1 mm being detected.

    DATA CONCLUSION: Improved sensitivities at lower FP can be achieved by co-training datasets via the CAVEAT paradigm to address the problem of data sparsity.

    LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

  7. Kazim AR, Subramaniam V, Houssaini J, Tappe D, Heo CC
    Vet Parasitol Reg Stud Reports, 2024 Jan;47:100965.
    PMID: 38199684 DOI: 10.1016/j.vprsr.2023.100965
    This paper describes a new tick-host record of Haemaphysalis wellingtoni from the helmeted guineafowl (Numida meleagris) in Peninsular Malaysia. This record is also the first report of a tick infestation from N. meleagris in Asia. A checklist of the tick-guineafowl associations has been designed, resulting in 32 tick species including H. wellingtoni recorded as infesting N. meleagris worldwide. A list of pathogens harboured or transmitted by H. wellingtoni is provided. The status of H. wellingtoni as a true parasite of N. meleagris, and the health threat posed to the guineafowls are discussed in this paper.
  8. Lau YL, Chang PY, Subramaniam V, Ng YH, Mahmud R, Ahmad AF, et al.
    Parasit Vectors, 2013 Sep 09;6(1):257.
    PMID: 24010903 DOI: 10.1186/1756-3305-6-257
    BACKGROUND: Sarcocystis species are protozoan parasites with a wide host range including snakes. Although there were several reports of Sarcocytis species in snakes, their distribution and prevalence are still not fully explored.

    METHODS: In this study, fecal specimens of several snake species in Malaysia were examined for the presence of Sarcocystis by PCR of 18S rDNA sequence. Microscopy examination of the fecal specimens for sporocysts was not carried as it was difficult to determine the species of the infecting Sarcocystis.

    RESULTS: Of the 28 snake fecal specimens, 7 were positive by PCR. BLASTn and phylogenetic analyses of the amplified 18S rDNA sequences revealed the snakes were infected with either S. nesbitti, S. singaporensis, S. zuoi or undefined Sarcocystis species.

    CONCLUSION: This study is the first to report Sarcocystis infection in a cobra, and S. nesbitti in a reticulated python.

  9. Ngatiman M, Jami MS, Abu Bakar MR, Subramaniam V, Loh SK
    Heliyon, 2021 Jan;7(1):e05931.
    PMID: 33490684 DOI: 10.1016/j.heliyon.2021.e05931
    The formation of struvite crystals or magnesium ammonium phosphate (MgNH4PO4) in palm oil mill effluent (POME) occurs as early as in the secondary stage of POME treatment system. Its growth continues in the subsequent tertiary treatment which reduces piping diameter, thus affecting POME treatment efficiency. Hypothesis. The beneficial use of the crystal is the motivation. This occurrence is rarely reported in scientific articles despite being a common problem faced by palm oil millers. The aim of this study is to characterize struvite crystals found in an anaerobic digester of a POME treatment facility in terms of their physical and chemical aspects. The compositions, morphology and properties of these crystals were determined via energy dispersive spectroscopy (EDS), elemental analysis, scanning electron microscopy (SEM) and x-ray diffraction (XRD). Solubility tests were carried out to establish solubility curve for struvite from POME. Finally, crystal growth experiment was done applying reaction crystallization method to demonstrate struvite precipitation from POME. Results showed that high phosphorous (P) (24.85 wt%) and magnesium (Mg) (21.33 wt%) content was found in the struvite sample. Elemental analysis detected carbon (C), hydrogen (H), nitrogen (N) and sulfur (S) below 4 wt%. The crystals analysed by XRD in this study were confirmed as struvite with 94.8% struvite mineral detected from its total volume. Having an orthorhombic crystal system, struvite crystals from POME recorded an average density of 1.701 g cm-3. Solubility curve of struvite from POME was established with maximum solubility of 275.6 mg L-1 at pH 3 and temperature 40 °C. Minimum solubility of 123.6 mg L-1 was recorded at pH 7 and temperature 25 °C. Crystal growth experiment utilizing POME as the source medium managed to achieve 67% reduction in phosphorous content. This study concluded that there is a potential of harnessing valuable nutrients from POME in the form of struvite. Struvite precipitation technology can be adapted in the management of POME in order to achieve maximum utilization of the nutrients that are still abundant in POME. At the same time maximization of nutrient extractions from POME will also reduce pollutants loading in the final discharge.
  10. Eusof Izzudin MP, Al–Bedri A, Subramaniam V, Matthews P, Cheong AT
    MyJurnal
    Depressive disorders are common. As compared to the general population, healthcare personnel are hypothesized to have an above than average risk to develop this condition. The aim of this study is to assess the prevalence of this condition and its contributing factors amongst primary healthcare personnel.
    Methods: A cross-sectional study was conducted by universally sampling 179 primary healthcare personnel at nine primary healthcare centers across Kuala Lumpur and Selangor in May 2015. Depressive symptoms were screened using self-administered Patient Health Questionnaire-9 (PHQ-9) questionnaire. Socio-demographic and work profile data were also assessed.
    Results: 92.7% of the 179 personnel agreed to participate. Near half of the respondents were staff nurses (49%), followed by doctors (22%), assistant medical officers (10%), attendants (10%) and the remaining were pharmacists, dieticians, and laboratory technicians (9%). Depression was found to be present in 38% of the participants with one-third found to have moderate to severe depression. Bivariate analysis show that males (p=0.043), assistant medical officers (p=0.048), and working more than 10 hours per day (p=0.019) are significant risk factors. Further analysis by logistic regression shows that working more than 10 hours per day increases the odds of depression by 3.1 (OR 3.1, 95% CI 1.1-8.7, p=0.03).
    Conclusions: A high prevalence of depression was found within the healthcare personnel population at the primary healthcare centres studied. Being a male, employed as an assistant medical officer, and, prolonged hours at the workplace is a significant risk factor for depression.
  11. Ng YH, Fong MY, Subramaniam V, Shahari S, Lau YL
    Res Vet Sci, 2015 Dec;103:201-4.
    PMID: 26679818 DOI: 10.1016/j.rvsc.2015.10.009
    Sarcocystis species are pathogenic parasites that infect a wide range of animals, including cattle. A high prevalence of cattle sarcocystosis has been reported worldwide, but its status is unknown in Malaysia. This study focused on utilizing 18S rDNA to identify Sarcocystis species in Malaysian cattle and to determine their genetic variants. In this study, only Sarcocystis cruzi was detected in Malaysian cattle. The intra-species S. cruzi phylogenetic tree analysis and principal coordinate analysis (PCoA), respectively displayed two minor groups among the parasite isolates. This finding was supported by high Wright FST value (FST=0.647). The definitive hosts (dogs) may play a fundamental role in the development of S. cruzi genetic variants. Additionally, the existence of microheterogeneity within the S. cruzi merozoites and/or distinct genetic variants arisen from independent merozoites in mature sarcocysts, possibly contributed to the existence of intra-species variations within the population.
  12. Kanadasan J, Fauzi AFA, Razak HA, Selliah P, Subramaniam V, Yusoff S
    Materials (Basel), 2015 Sep 22;8(9):6508-6530.
    PMID: 28793579 DOI: 10.3390/ma8095319
    The agricultural industry in Malaysia has grown rapidly over the years. Palm oil clinker (POC) is a byproduct obtained from the palm oil industry. Its lightweight properties allows for its utilization as an aggregate, while in powder form as a filler material in concrete. POC specimens obtained throughout each state in Malaysia were investigated to evaluate the physical, chemical, and microstructure characteristics. Variations between each state were determined and their possible contributory factors were assessed. POC were incorporated as a replacement material for aggregates and their engineering characteristics were ascertained. Almost 7% of density was reduced with the introduction of POC as aggregates. A sustainability assessment was made through greenhouse gas emission (GHG) and cost factor analyses to determine the contribution of the addition of POC to the construction industry. Addition of POC helps to lower the GHG emission by 9.6% compared to control specimens. By channeling this waste into the construction industry, an efficient waste-management system can be promoted; thus, creating a cleaner environment. This study is also expected to offer some guides and directions for upcoming research works on the incorporation of POC.
  13. Amir A, Russell B, Liew JW, Moon RW, Fong MY, Vythilingam I, et al.
    Sci Rep, 2016 Apr 21;6:24623.
    PMID: 27097521 DOI: 10.1038/srep24623
    Plasmodium knowlesi is extensively used as an important malaria model and is now recognized as an important cause of human malaria in Malaysia. The strains of P. knowlesi currently used for research were isolated many decades ago, raising concerns that they might no longer be representative of contemporary parasite populations. We derived a new P. knowlesi line (University Malaya line, UM01), from a patient admitted in Kuala Lumpur, Malaysia, and compared it with a human-adapted laboratory line (A1-H.1) derived from the P. knowlesi H strain. The UM01 and A1-H.1 lines readily invade human and macaque (Macaca fascicularis) normocytes with a preference for reticulocytes. Whereas invasion of human red blood cells was dependent on the presence of the Duffy antigen/receptor for chemokines (DARC) for both parasite lines, this was not the case for macaque red blood cells. Nonetheless, differences in invasion efficiency, gametocyte production and the length of the asexual cycle were noted between the two lines. It would be judicious to isolate and characterise numerous P. knowlesi lines for use in future experimental investigations of this zoonotic species.
  14. Gnanasegaran N, Govindasamy V, Simon C, Gan QF, Vincent-Chong VK, Mani V, et al.
    Eur J Clin Invest, 2017 Mar 30.
    PMID: 28369799 DOI: 10.1111/eci.12753
    BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic (DA-ergic) neurons in the substantia nigra (SN) and represented as a huge threat to the geriatric population. Cell replacement therapies (CRTs) have been proposed as a promising strategy to slow down or replace neuronal loss. Among the widely available cell sources, dental pulp stem cells (DPSCs) portray as an attractive source primarily due to their neural crest origin, ease of tissue procurement and less ethical hurdles.

    MATERIALS AND METHODS: We first demonstrated the in vitro differentiation ability of DPSCs towards DA-ergic-like cells before evaluating their neuro-protection/neuro-restoration capacities in MPTP-induced mice. Transplantation via intrathecal was performed with behavioural assessments being evaluated every fortnight. Subsequent analysis investigating their immuno-modulatory behaviour was conducted using neuronal and microglial cell lines.

    RESULTS: It was apparent that the behavioural parameters began to improve corresponding to tyrosine hydroxylase (TH), dopamine transporter (DAT) and dopamine decarboxylase (AADC) immunostaining in SN and striatum as early as 8-week post-transplantation (P < 0·05). About 60% restoration of DA-ergic neurons was observed at SN in MPTP-treated mice after 12-week post-transplantation. Similarly, their ability to reduce toxic effects of MPTP (DNA damages, reactive oxygen species and nitric oxide release) and regulate cytokine levels was distinctly noted (P < 0·05) upon exposure in in vitro model.

    CONCLUSIONS: Our results suggest that DPSCs may provide a therapeutic benefit in the old-aged PD mice model and may be explored in stem cell-based CRTs especially in geriatric population as an attempt towards 'personalized medicine'.

  15. Subramaniam V, Ng BK, Phon SE, Muhammad Rafi'uddin H, Wira Sorfan AR, Siti Hajar AA, et al.
    Life (Basel), 2023 Jun 30;13(7).
    PMID: 37511865 DOI: 10.3390/life13071491
    BACKGROUND: COVID-19 is an emerging global pandemic with potential adverse effects during pregnancy. This study aimed to determine the adverse maternal and foetal outcomes due to COVID-19 infection. We also compared maternal and neonatal outcomes with regard to the timing of diagnosis (first and second trimester vs. third and fourth trimester); early COVID-19 (stage I and II) vs. severe-stage COVID-19 (III, IV, and V); and lastly, women who were partially vaccinated vs. unvaccinated.

    METHODS: This was a retrospective study conducted in HCTM from January 2021 to January 2022. All pregnant women admitted for COVID-19 infections were recruited. The patients' records were traced. Adverse maternal and neonatal outcomes were documented and analysed.

    RESULTS: There were 172 pregnant women recruited into this study. We excluded twenty-four patients with incomplete data and nine women who delivered elsewhere. The final 139 patients were available for data analysis. The majority of women were in their third trimester of pregnancy (87.8%); however, only 5.0% and 7.2% were in the first and second trimesters, respectively. The study population had a median BMI of 29.1 kg/m2 and almost half of them had never received a COVID-19 vaccination. A sub-analysis of data concerning adverse maternal and foetal outcomes comparing early vs. severe stages of COVID-19 infection showed that severe-stage disease increased the risk of preterm birth (54.5% vs. 15.4%, p < 0.001) and preterm birth before 34 weeks (31.9% vs. 2.6%, p < 0.001) significantly. The severe-stage disease also increased NICU admission (40.9% vs. 15.4%, p = 0.017) with lower birth weight (2995 g vs. 2770 g, p = 0.017). The unvaccinated mothers had an increased risk of preterm birth before 34 weeks and this was statistically significant (11.6% vs. 2.9%, p = 0.048).

    CONCLUSIONS: Adverse pregnancy outcomes such as ICU admission or patient death could occur; however, the clinical course of COVID-19 in most women was not severe and the infection did not significantly influence the pregnancy. The risk of preterm birth before 34 weeks was higher in a more severe-stage disease and unvaccinated mother. The findings from this study can guide and enhance antenatal counselling of women with COVID-19 infection, although they should be interpreted with caution in view of the very small number of included cases of patients in the first and second trimesters.

  16. Akram U, McCarty K, Akram A, Gardani M, Tan A, Villarreal D, et al.
    Sleep Health, 2018 08;4(4):360-363.
    PMID: 30031529 DOI: 10.1016/j.sleh.2018.04.005
    OBJECTIVES: Type D personality is characterized by the combination of social inhibition and negative affectivity. This study examined the relationship between Type D personality and insomnia symptoms amongst a sample of the general-population.

    METHODS: Adults from the general-population (n = 392) completed online measures of Type D personality (DS14) and insomnia severity.

    RESULTS: Individuals with the Type D personality trait reported significantly greater symptoms of insomnia relative to Non-Type Ds. Moreover, insomnia-symptoms were independently related to negative affectivity (NA) and social inhibition (SI) and the Type D interaction (i.e. synergistic product of SI and NA). Linear regression analysis determined that NA but not SI significantly predicted insomnia symptoms after controlling for age and sex. However, after accounting for the Type D interaction, negative affectivity remained the only significant predictor of insomnia-symptoms.

    CONCLUSIONS: The Type D personality type appears to be related to insomnia-symptoms, both as a categorical and dimensional construct. These outcomes support prior research evidencing that whilst Type D personality is related to poor sleep in adolescents, NA appears to be the main contributor.

  17. 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.

  18. Ang GY, Yu CY, Subramaniam V, Abdul Khalid MI, Tuan Abdu Aziz TA, Johari James R, et al.
    PLoS One, 2016;11(10):e0164169.
    PMID: 27798644 DOI: 10.1371/journal.pone.0164169
    The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme's activity have been identified and catalogued in the CYP allele nomenclature database. In this study, we investigated the presence of well-established variants as well as novel polymorphisms in the CYP2C19 gene of 62 Orang Asli from the Peninsular Malaysia. A total of 449 genetic variants were detected including 70 novel polymorphisms; 417 SNPs were located in introns, 23 in upstream, 7 in exons, and 2 in downstream regions. Five alleles and seven genotypes were inferred based on the polymorphisms that were found. Null alleles that were observed include CYP2C19*3 (6.5%), *2 (5.7%) and *35 (2.4%) whereas allele with increased function *17 was detected at a frequency of 4.8%. The normal metabolizer genotype was the most predominant (66.1%), followed by intermediate metabolizer (19.4%), rapid metabolizer (9.7%) and poor metabolizer (4.8%) genotypes. Findings from this study provide further insights into the CYP2C19 genetic profile of the Orang Asli as previously unreported variant alleles were detected through the use of massively parallel sequencing technology platform. The systematic and comprehensive analysis of CYP2C19 will allow uncharacterized variants that are present in the Orang Asli to be included in the genotyping panel in the future.
  19. Teh LK, Subramaniam V, Tuan Abdu Aziz TA, Lee LS, Ismail MI, Yu CY, et al.
    Drug Metab. Pharmacokinet., 2016 Aug;31(4):304-13.
    PMID: 27325019 DOI: 10.1016/j.dmpk.2016.04.004
    We conducted a systematic characterization of CYP2C9 variants in 61 Orang Asli and 96 Singaporean Malays using the whole genome sequences data and compared the variants with the other 11 HapMap populations. The frequency of rs1057910 (CYP2C9*3) is the highest in the Orang Asli compared to other populations. Three alleles with clinical implication were detected in the Orang Asli while 2 were found in the Singaporean Malays. Large numbers of the Orang Asli are predicted to have reduced metabolic capacity and therefore they would require a lower dose of drugs which are metabolized by CYP2C9. They are also at increased risks of adverse effects and therapeutic failures. A large number of CYP2C9 variants in the Orang Asli were not in the Hardy Weinberg Equilibrium which could be due to small sample size or mutations that disrupt the equilibrium of allele frequencies. In conclusion, different polymorphism patterns, allele frequencies, genotype frequencies and LD blocks are observed between the Orang Asli, the Singaporean Malays and the other populations. The study provided new information on the genetic polymorphism of CYP2C9 which is important for the implementation of precision medicine for the Orang Asli.
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