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  1. Fulltext Identification of novel pathogenic copy number aberrations in multiple myeloma: the Malaysian context
    Ivyna Bong PN, Ng CC, Lam KY, Megat Baharuddin PJ, Chang KM, Zakaria Z
    Mol Cytogenet, 2014;7(1):24.
    PMID: 24690091 DOI: 10.1186/1755-8166-7-24
    Multiple myeloma is an incurable disease. Little is known about the genetic and molecular mechanisms governing the pathogenesis of multiple myeloma. The risk of multiple myeloma predispositions varies among different ethnicities. More than 50% of myeloma cases showed normal karyotypes with conventional cytogenetic analysis due to the low mitotic activity and content of plasma cells in the bone marrow. In the present study, high resolution array comparative genomic hybridization technique was used to identify copy number aberrations in 63 multiple myeloma patients of Malaysia.
  2. Fulltext MicroRNA expression patterns and target prediction in multiple myeloma development and malignancy
    Bong IPN, Ng CC, Baharuddin P, Zakaria Z
    Genes Genomics, 2017;39(5):533-540.
    PMID: 28458781 DOI: 10.1007/s13258-017-0518-7
    Epigenetic changes have emerged as key causes in the development and progression of multiple myeloma (MM). In this study, global microRNA (miRNA) expression profiling were performed for 27 MM (19 specimens and 8 cell lines) and 3 normal controls by microarray. miRNA-targets were identified by integrating the miRNA expression profiles with mRNA expression profiles of the matched samples (unpublished data). Two miRNAs were selected for verification by RT-qPCR (miR-150-5p and miR-4430). A total of 1791 and 8 miRNAs were over-expressed and under-expressed, respectively in MM compared to the controls (fold change ≥2.0; p 
  3. Fulltext Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study
    Bong IP, Ng CC, Fakiruddin SK, Lim MN, Zakaria Z
    Bosn J Basic Med Sci, 2016 Nov 10;16(4):268-275.
    PMID: 27754828 DOI: 10.17305/bjbms.2016.1568
    Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA)-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05). NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05). Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01). Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM.
  4. Fulltext An ecological transcriptome approach to capture the molecular and physiological mechanisms of mass flowering in Shorea curtisii
    Suhaimi AH, Kobayashi MJ, Satake A, Ng CC, Lee SL, Muhammad N, et al.
    PeerJ, 2023;11:e16368.
    PMID: 38047035 DOI: 10.7717/peerj.16368
    Climatic factors have commonly been attributed as the trigger of general flowering, a unique community-level mass flowering phenomenon involving most dipterocarp species that forms the foundation of Southeast Asian tropical rainforests. This intriguing flowering event is often succeeded by mast fruiting, which provides a temporary yet substantial burst of food resources for animals, particularly frugivores. However, the physiological mechanism that triggers general flowering, particularly in dipterocarp species, is not well understood largely due to its irregular and unpredictable occurrences in the tall and dense forests. To shed light on this mechanism, we employed ecological transcriptomic analyses on an RNA-seq dataset of a general flowering species, Shorea curtisii (Dipterocarpaceae), sequenced from leaves and buds collected at multiple vegetative and flowering phenological stages. We assembled 64,219 unigenes from the transcriptome of which 1,730 and 3,559 were differentially expressed in the leaf and the bud, respectively. Differentially expressed unigene clusters were found to be enriched with homologs of Arabidopsis thaliana genes associated with response to biotic and abiotic stresses, nutrient level, and hormonal treatments. When combined with rainfall data, our transcriptome data reveals that the trees were responding to a brief period of drought prior to the elevated expression of key floral promoters and followed by differential expression of unigenes that indicates physiological changes associated with the transition from vegetative to reproductive stages. Our study is timely for a representative general flowering dipterocarp species that occurs in forests that are under the constant threat of deforestation and climate change as it pinpoints important climate sensitive and flowering-related homologs and offers a glimpse into the cascade of gene expression before and after the onset of floral initiation.
  5. Baska mask versus endotracheal tube in laparoscopic cholecystectomy surgery: a prospective randomized trial
    Ng CC, Sybil Shah MHB, Chaw SH, Mansor MB, Tan WK, Koong JK, et al.
    Expert Rev Med Devices, 2021 Feb;18(2):203-210.
    PMID: 33322949 DOI: 10.1080/17434440.2021.1865796
    Background: Supraglottic airway devices have increasingly been used as the airway technique of choice in laparoscopic surgeries. This study compared the efficacy and safety of the Baska Mask with endotracheal tube (ETT) in patients undergoing elective laparoscopic cholecystectomy.Research design and methods: This single-center, prospective, randomized controlled trial recruited 60 patients aged 18-75 years with American Society of Anesthesiologists' classifications I to III. The time taken to achieve effective airway, number of attempts, ease of insertion, ventilation parameters, hemodynamics data, and pharyngolaryngeal complications were recorded.Results: The time taken to achieve effective airway was shorter for the Baska group (26.6 ± 4.7 vs. 47.2 ± 11.8 s; p
  6. Is pre-stroke frailty as determined by the Clinical Frailty Scale version 2.0 associated with stroke outcomes?
    Ng CC, Lim WC, Tan KM, Wong KY, Kanagarajah RR, Singh HSAK, et al.
    Singapore Med J, 2023 Mar 06.
    PMID: 36926745 DOI: 10.4103/singaporemedj.SMJ-2021-187
  7. Fulltext A novel and non-invasive approach utilising nasal washings for the detection of nasopharyngeal carcinoma
    Tan GW, Sivanesan VM, Abdul Rahman FI, Hassan F, Hasbullah HH, Ng CC, et al.
    Int J Cancer, 2019 Oct 15;145(8):2260-2266.
    PMID: 30698824 DOI: 10.1002/ijc.32173
    Nasopharyngeal carcinoma (NPC) is an epithelial cancer of the nasopharynx which is highly associated with Epstein-Barr virus (EBV). Worldwide, most of the top 20 countries with the highest incidence and mortality rates of NPC are low- and middle-income countries. Many studies had demonstrated that EBV could be detected in the tissue, serum and plasma of NPC patients. In this study, we explored the potential of assays based on non-invasive nasal washings (NW) as a diagnostic and prognostic tool for NPC. A total of 128 patients were evaluated for NW EBV DNA loads and a subset of these samples were also tested for 27 EBV and human miRNAs shortlisted from literature. EBV DNA and seven miRNAs showed area under the receiver operating characteristic curve (AUC) values of more than 0.7, suggestive of their potential utility to detect NPC. Logistic regression analyses suggested that combination of two NW assays that test for EBNA-1 and hsa-miR-21 had the best performance in detecting NPC. The trend of NW EBV DNA load matched with clinical outcome of 71.4% (10 out of 14) NPC patients being followed-up. In summary, the non-invasive NW testing panel may be particularly useful for NPC screening in remote areas where healthcare facilities and otolaryngologists are lacking, and may encourage frequent testing of individuals in the high risk groups who are reluctant to have their blood tested. However, further validation in an independent cohort is required to strengthen the utility of this testing panel as a non-invasive detection tool for NPC.
  8. Ethnic variation of genetic (idiopathic) generalized epilepsy in Malaysia
    Lim KS, Ng CC, Chan CK, Foo WS, Low JS, Tan CT
    Seizure, 2017 Feb;45:24-27.
    PMID: 27912112 DOI: 10.1016/j.seizure.2016.11.011
    PURPOSE: Ethnic variation in epilepsy classification was reported in the Epilepsy Phenome/Genome Project. This study aimed to determine the ethnic variation in the prevalence of genetic (idiopathic) generalized epilepsy (GGE) and GGE with family history in a multi-ethnic Asian population in Malaysia.

    METHOD: In this cross-sectional study, 392 patients with a clinical diagnosis of GGE were recruited in the neurology outpatient clinic, University of Malaya Medical Centre (UMMC), from January 2011 till April 2016.

    RESULTS: In our epilepsy cohort (n=2100), 18.7% were diagnosed to have GGE. Of those, 28.6% >(N=112) had family history of epilepsy with a mean age of seizure onset of 16.5 years old, and 42.0% had myoclonic seizures (N=47). The lifetime prevalence of epilepsy among first-degree relative of those with GGE and positive family history was 15.0%. Analysis according to ethnicity showed that Malaysian Chinese had the lowest percentage of GGE among those with epilepsy (12.3%), as compared with Indian and Malay (25.3% and 21.3%, p<0.001). In addition, 32.1% of these Indian patients with GGE had positive family history, which is more than the Malay (26.4%) and Chinese (27.5%) ethnic groups. Consanguineous marriage was noted in 5 Indian families with positive family history (9.6%).

    CONCLUSION: There was ethnic variation in the prevalence of GGE, whereby the Malaysian Chinese had the lowest percentage of GGE as compared with Indian and Malay. A substantial proportion of GGE had positive family history among the three ethnics groups.

    Study site: neurology outpatient clinic, University of Malaya Medical Centre (UMMC)
  9. An Overview of Culinary and Medicinal Mushrooms in Neurodegeneration and Neurotrauma Research
    Wong KH, Ng CC, Kanagasabapathy G, Yow YY, Sabaratnam V
    Int J Med Mushrooms, 2017;19(3):191-202.
    PMID: 28605334 DOI: 10.1615/IntJMedMushrooms.v19.i3.10
    Culinary and medicinal mushrooms have been appreciated since prehistoric times as valuable resources for food and medicine. Edible mushrooms represent an untapped source of nutraceuticals and valuable palatable food. Long considered tonics, they are now treasured as functional foods that can improve human health and quality of life. Numerous studies have provided insights into the neuroprotective effects of edible mushrooms, which are attributed to their antioxidant, antineuroinflammatory, and cholinesterase inhibitory properties, and their ability to prevent neuronal death. Here we review the recent literature on the role of culinary and medicinal mushrooms in the management of neurodegenerative diseases and neurotrauma. We highlight some of the molecular mechanisms for how these alternative medicines provide health benefits that could help us to harness their neuroprotective effects.
  10. Prostaglandin-endoperoxide synthase (PTGS2) and Defensin beta 1 (DEFB1) gene polymorphisms are not associated with periodontitis in Malays
    Jagender Singh JK, Vaithilingam RD, Ng CC, Baharuddin NA, Hasnur Safii S, Rahman MT
    Malays J Pathol, 2021 Dec;43(3):425-434.
    PMID: 34958064
    INTRODUCTION: In line with the association of prostaglandin-endoperoxide synthase 2 (PTGS2) and defensin beta 1 (DEFB1) single nucleotide polymorphisms (SNPs) with periodontitis among the Chinese and European populations, the current study was aimed to assess the same association among the Malays in Malaysia.

    METHODS: Blood samples of individuals with periodontitis (PD) (n=72) and periodontally healthy (PH) (n=62) donors were obtained from Malaysian Periodontal Database and Biobanking system (MPDBS). Genomic DNA samples were analyzed for three PTGS2 SNPs (rs5275, rs20417, rs689466,) and one DEFB1 SNP (rs1047031) using Taqman SNP genotyping assays. Notably, rs20417 and rs689466 were located in the promoter region while rs5275 and rs1047031 were located in the 3' untranslated region of the transcript. Association between the SNPs and PD were then analyzed using genotypic association analysis (additive, dominant and recessive models).

    RESULTS: The allelic frequency for the rs689466-G was higher in PD group (35.2%) compared that in PH group (29.0%). However, the association of rs689466-G and other SNPs with PD was not statistically significant (at 95% CI). No associations were observed for genotypic associations between the PTGS2 and DEFB1 SNPs with PD susceptibility.

    CONCLUSIONS: PTGS2 (rs5275, rs20417, and rs689466) and DEFB1 (rs1047031) polymorphism was not associated with PD in Malays, unlike the Chinese, Taiwanese & European population. This suggests that other causal variants might be involved in the development and progression of PD among Malays.

  11. Fulltext Profiling lysophosphatidic acid levels in plasma from head and neck cancer patients
    Abdul Rahman M, Mohamad Haron DE, Hollows RJ, Abdul Ghani ZDF, Ali Mohd M, Chai WL, et al.
    PeerJ, 2020;8:e9304.
    PMID: 32547888 DOI: 10.7717/peerj.9304
    Head and neck squamous cell carcinoma (HNSCC) represents a significant world health problem, with approximately 600,000 new cases being diagnosed annually. The prognosis for patients with HNSCC is poor and, therefore, the identification of biomarkers for screening, diagnosis and prognostication would be clinically beneficial. A limited number of studies have used lipidomics to profile lipid species in the plasma of cancer patients. However, the profile and levels of lysophosphatidic acid (LPA) species have not been examined in HNSCC. In this study, a targeted lipidomics approach using liquid chromatography triple quadrupole mass spectrometry (LCMS/MS) was used to analyse the concentration of LPA (16:0 LPA, 18:0 LPA, 18:1 LPA, 18:2 LPA and 20:4 LPA) in the plasma of patients with oral squamous cell carcinoma (OSCC) and nasopharyngeal carcinoma (NPC), together with healthy controls. The levels of three LPA species (18:1 LPA, 18:2 LPA and 20:4 LPA) were significantly lower in the plasma of OSCC patients, whilst the concentrations of all five LPA species tested were significantly lower in plasma from NPC patients. Furthermore, the order of abundance of LPA species in plasma was different between the control and cancer groups, with 16:0 LPA, 18:0 LPA levels being more abundant in OSCC and NPC patients. Medium to strong correlations were observed using all pairs of LPA species and a clear separation of the normal and tumour groups was observed using PCA analysis. In summary, the results of this study showed that the levels of several LPA species in the plasma of patients with OSCC and NPC were lower than those from healthy individuals. Understanding these variations may provide novel insights into the role of LPA in these cancers.
  12. Fulltext Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy: a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications
    Rubboli G, Beier CP, Selmer KK, Syvertsen M, Shakeshaft A, Collingwood A, et al.
    Brain Commun, 2023;5(3):fcad182.
    PMID: 37361715 DOI: 10.1093/braincomms/fcad182
    Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.
  13. Fulltext Sex-specific disease modifiers in juvenile myoclonic epilepsy
    Shakeshaft A, Panjwani N, Collingwood A, Crudgington H, Hall A, Andrade DM, et al.
    Sci Rep, 2022 Feb 21;12(1):2785.
    PMID: 35190554 DOI: 10.1038/s41598-022-06324-2
    Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p 
  14. Fulltext COVID-19 Infection among Older People Admitted to Hospital: A Cross-Sectional Analysis
    Thiam CN, Hasmukharay K, Lim WC, Ng CC, Pang GHM, Abdullah A, et al.
    Geriatrics (Basel), 2021 Mar 08;6(1).
    PMID: 33800304 DOI: 10.3390/geriatrics6010025
    (1) Background: Older people with COVID-19 infection report worse clinical outcomes. There is a paucity of local data and this study aimed to describe the clinical progression of older people admitted to a university hospital in Malaysia with COVID-19 infection. (2) Methods: Older people (≥60 years) admitted with COVID-19 infection confirmed with RT-PCR from 27 February 2020-25 May 2020 were included in this study. Data on patient characteristics, hospital treatment, and inpatient outcomes were collected via hospital-held electronic medical records. Analysis was done to describe the cohort and identify factors associated with inpatient mortality. (3) Results: 26 participants were included (mean age 76.2 years, female 57.7%). All had at least one comorbid condition and half were frail. About 19.2% had non-respiratory (atypical) symptoms; 23.1% had a severe disease that required intensive care unit monitoring; 46.2% were given COVID-19 targeted therapy. Inpatient mortality and overall complication rates were 23.1% and 42.3%, respectively. Delirium on presentation and lower Ct-value were associated with mortality. (4) Conclusions: Older people with COVID-19 infection have severe infection and poor hospital outcomes. Vigilant hospital care is necessary to address their multimorbidity and frailty, along with appropriate treatment for their infection.
  15. Fulltext JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma
    Nairismägi ML, Tan J, Lim JQ, Nagarajan S, Ng CC, Rajasegaran V, et al.
    Leukemia, 2016 06;30(6):1311-9.
    PMID: 26854024 DOI: 10.1038/leu.2016.13
    Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
  16. Fulltext A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci
    Low JS, Chin YM, Mushiroda T, Kubo M, Govindasamy GK, Pua KC, et al.
    PLoS One, 2016;11(1):e0145774.
    PMID: 26730743 DOI: 10.1371/journal.pone.0145774
    BACKGROUND: Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition.

    METHODS: A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).

    RESULTS: Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes.

    CONCLUSION: Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

  17. Fulltext HLA-B*15:02 association with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in an Indian population: a pooled-data analysis and meta-analysis
    Khor AH, Lim KS, Tan CT, Wong SM, Ng CC
    Epilepsia, 2014 Nov;55(11):e120-4.
    PMID: 25266342 DOI: 10.1111/epi.12802
    This study aimed to investigate the prevalence and association of HLA-B*15:02 with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-SJS/TEN) in the Indian population in Malaysia, which mostly originated from Southern India. HLA-B alleles in five Indian case patients with CBZ-SJS/TEN and 52 CBZ-tolerant controls, and followed by a pooled sample of seven cases from two centers in Malaysia were analyzed. Positive association for HLA-B*15:02 with CBZ-SJS/TEN was detected in Indians (40% [2/5] vs. 3.8% [2/52], odds ratio [OR] 16.7, p = 0.0349), of which 80% (4/5) of the Indian patients originated from Southern India. A pooled sample of seven cases showed stronger association between HLA-B*15:02 and CBZ-SJS/TEN (57.1% [4/7] vs. 3.8% [2/52], OR 33.3, 95% confidence interval [CI] 4.25-162.21, p = 1.05 × 10(-3)). Subsequent meta-analysis on Indians from Malaysia and India further demonstrated a significant and strong association between HLA-B*15:02 and CBZ-SJS/TEN (OR 38.54; 95% CI 6.83-217.34, p < 1.0 × 10(-4)). Our study is the first on Indians predominantly from Southern India that demonstrated HLA-B*15:02 as a strong risk factor for CBZ-SJS/TEN despite a low population allele frequency. This stressed the importance of testing for HLA-B*15:02, irrespective of the ancestral background, including populations with low allele frequency.
  18. Fulltext HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese
    Chin YM, Mushiroda T, Takahashi A, Kubo M, Krishnan G, Yap LF, et al.
    Int J Cancer, 2015 Feb 1;136(3):678-87.
    PMID: 24947555 DOI: 10.1002/ijc.29035
    Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p = 1.73 × 10(-9)). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p(HLA-A-aa-site-99) = 3.79 × 10(-8), p(rs1136697) = 3.79 × 10(-8)) and T-cell receptor binding site (p(HLA-A-aa-site-145) = 1.41 × 10(-4), p(rs1059520) = 1.41 × 10(-4)) of the HLA-A. We also detected strong association signals in the 5'-UTR region with predicted active promoter states (p(rs41545520) = 7.91 × 10(-8)). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A*11:01, and to a lesser extent HLA-A*02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese.
  19. Fulltext Isolation and characterization of microsatellite loci in an endangered palm, Johannesteijsmannia lanceolata (Arecaceae)
    Ang CC, Lee SL, Lee CT, Tnah LH, Zakaria RM, Ng CC
    Am J Bot, 2011 May;98(5):e117-9.
    PMID: 21613176 DOI: 10.3732/ajb.1000494
    Microsatellite markers were developed for Johannesteijsmannia lanceolata to assess the genetic diversity and mating system of this alarmingly endangered species.
  20. Epstein-Barr virus-encoded latent membrane protein-1 upregulates 14-3-3σ and Reprimo to confer G(2)/M phase cell cycle arrest
    Yeo KS, Mohidin TB, Ng CC
    C. R. Biol., 2012 Dec;335(12):713-21.
    PMID: 23312294 DOI: 10.1016/j.crvi.2012.11.002
    Epstein-Barr virus (EBV) is a ubiquitous tumor-causing virus which infects more than 90% of the world population asymptomatically. Recent studies suggest that LMP-1, -2A and -2B cooperate in the tumorigenesis of EBV-associated epithelial cancers such as nasopharygeal carcinoma, oral and gastric cancer. In this study, LMPs were expressed in the HEK293T cell line to reveal their oncogenic mechanism via investigation on their involvement in the regulation of the cell cycle and genes that are involved. LMPs were expressed in HEK293T in single and co-expression manner. The transcription of cell cycle arrest genes were examined via real-time PCR. Cell cycle progression was examined via flow cytometry. 14-3-3σ and Reprimo were upregulated in all LMP-1 expressing cells. Moreover, cell cycle arrest at G(2)/M progression was detected in all LMP-1 expressing cells. Therefore, we conclude that LMP-1 may induce cell cycle arrest at G(2)/M progression via upregulation of 14-3-3σ and Reprimo.
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