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Fulltext X-chromosome association study reveals genetic susceptibility loci of nasopharyngeal carcinoma

Zuo XY, Feng QS, Sun J, Wei PP, Chin YM, Guo YM, et al.

Biol Sex Differ, 2019 03 25;10(1):13.
PMID: 30909962 DOI: 10.1186/s13293-019-0227-9

BACKGROUND: The male predominance in the incidence of nasopharyngeal carcinoma (NPC) suggests the contribution of the X chromosome to the susceptibility of NPC. However, no X-linked susceptibility loci have been examined by genome-wide association studies (GWASs) for NPC by far.
METHODS: To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716).
RESULTS: Firstly, the proportion of variance of X-linked loci over phenotypic variance was estimated in the discovery samples, which revealed that the phenotypic variance explained by X chromosome polymorphisms was estimated to be 12.63% (non-dosage compensation model) in males, as compared with 0.0001% in females. This suggested that the contribution of X chromosome to the genetic variance of NPC should not be neglected. Secondly, association analysis revealed that rs5927056 in DMD gene achieved X chromosome-wide association significance in the discovery sample (OR = 0.81, 95% CI 0.73-0.89, P = 1.49 × 10-5). Combined analysis revealed rs5927056 for DMD gene with suggestive significance (P = 9.44 × 10-5). Moreover, the female-specific association of rs5933886 in ARHGAP6 gene (OR = 0.62, 95%CI: 0.47-0.81, P = 4.37 × 10-4) was successfully replicated in Taiwan Chinese (P = 1.64 × 10-2). rs5933886 also showed nominally significant gender × SNP interaction in both Guangdong (P = 6.25 × 10-4) and Taiwan datasets (P = 2.99 × 10-2).
CONCLUSION: Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.
Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes

Chan CK, Low JS, Lim KS, Low SK, Tan CT, Ng CC

Neurol Sci, 2020 Mar;41(3):591-598.
PMID: 31720899 DOI: 10.1007/s10072-019-04122-9

INTRODUCTION: Genetic (idiopathic) generalized epilepsy (GGE) is a common form of epilepsy characterized by unknown aetiology and a presence of genetic component in its predisposition.
METHODS: To understand the genetic factor in a family with GGE, we performed whole exome sequencing (WES) on a trio of a juvenile myoclonic epilepsy/febrile seizure (JME/FS) proband with JME/FS mother and healthy father. Sanger sequencing was carried out for validation of WES results and variant detection in other family members.
RESULTS: Predictably damaging variant found in affected proband and mother but absent in healthy father in SCN1A gene was found to be associated with generalized epilepsy and febrile seizure. The novel non-synonymous substitution (c.5753C>T, p.S1918F) in SCN1A was found in all family members with GGE, of which 4/8 were JME subtypes, and/or febrile seizure, while 3 healthy family member controls did not have the mutation. This mutation was also absent in 41 GGE patients and 414 healthy Malaysian Chinese controls.
CONCLUSION: The mutation is likely to affect interaction between the sodium channel and calmodulin and subsequently interrupt calmodulin-dependent modulation of the channel.
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.
Fulltext Using DNA Barcodes to Aid the Identification of Larval Fishes in Tropical Estuarine Waters (Malacca Straits, Malaysia)

Chu C, Loh KH, Ng CC, Ooi AL, Konishi Y, Huang SP, et al.

Zool Stud, 2019;58:e30.
PMID: 31966331 DOI: 10.6620/ZS.2019.58-30

Larval descriptions of tropical marine and coastal fishes are very few, and this taxonomic problem is further exacerbated by the high diversity of fish species in these waters. Nonetheless, accurate larval identification in ecological and early life history studies of larval fishes is crucial for fishery management and habitat protection. The present study aimed to evaluate the usefulness of DNA barcodes to support larval fish identification since conventional dichotomous keys based on morphological traits are not efficient due to the lack of larval traits and the rapid morphological changes during ontogeny. Our molecular analysis uncovered a total of 48 taxa (21 families) from the larval samples collected from the Klang Strait waters encompassing both spawning and nursery grounds of marine and estuarine fishes. Thirty-two (67%) of the larval taxa were identified at the species level, two taxa (4%) at the genus level, and 14 taxa (29%) at family level. The relatively low rate of species-level identification is not necessarily due to the DNA barcoding method per se, but a general lack of reference sequences for speciose and non- commercial fish families such as Gobiidae, Blenniidae, and Callionymidae. Larval morphology remains important in species diagnoses when molecular matches are ambiguous. A lower ethanol percentage (50%) for larva preservation is also useful to keep the body of larvae intact for morphological identification, and to preserve DNA for subsequent molecular analyses. The 10% Chelex resin used to extract DNA is also cost- effective for long term monitoring of larval fishes. Hence, the DNA barcoding method is an effective and easy way to aid the identification of estuarine larval fishes at the species level.
Ultrasound-guided central venous vascular access-novel needle navigation technology compared with conventional method: A randomized study

Chew SC, Beh ZY, Hakumat Rai VR, Jamaluddin MF, Ng CC, Chinna K, et al.

J Vasc Access, 2020 Jan;21(1):26-32.
PMID: 31148509 DOI: 10.1177/1129729819852057

PURPOSE: Central venous catheter insertion is a common procedure in the intensive care setting. However, complications persist despite real-time ultrasound guidance. Recent innovation in needle navigation technology using guided positioning system enables the clinician to visualize the needle's real-time position and trajectory as it approaches the target. We hypothesized that the guided positioning system would improve performance time in central venous catheter insertion.
METHODS: A prospective randomized study was conducted in a single-center adult intensive care unit. In total, 100 patients were randomized into two groups. These patients underwent internal jugular vein central venous catheter cannulation with ultrasound guidance (short-axis scan, out-of-plane needling approach) in which one group adopted conventional method, while the other group was aided with the guided positioning system. Outcomes were measured by procedural efficacy (success rate, number of attempts, time to successful cannulation), complications, level of operators' experience, and their satisfaction.
RESULTS: All patients had successful cannulation on the first attempt except for one case in the conventional group. The median performance time for the guided positioning system method was longer (25.5 vs 15.5 s; p = 0.01). And 86% of the operators had more than 3-year experience in anesthesia. One post-insertion hematoma occurred in the conventional group. Only 88% of the operators using the guided positioning system method were satisfied compared to 100% in the conventional group.
CONCLUSION: Ultrasound-guided central venous catheter insertion via internal jugular vein was a safe procedure in both conventional and guided positioning system methods. The guided positioning system did not confer additional benefit but was associated with slower performance time and lower satisfaction level among the experienced operators.
Tranexamic Acid in Pediatric Scoliosis Surgery: A Prospective Randomized Trial Comparing High-dose and Low-dose Tranexamic Acid in Adolescent Idiopathic Scoliosis Undergoing Posterior Spinal Fusion Surgery

Hasan MS, Yunus SN, Ng CC, Chan CYW, Chiu CK, Kwan MK

Spine (Phila Pa 1976), 2021 Nov 15;46(22):E1170-E1177.
PMID: 33882541 DOI: 10.1097/BRS.0000000000004076

STUDY DESIGN: Prospective randomized double-blinded trial.
OBJECTIVE: The objective of this study is to determine the efficacy of high-dose versus low-dose tranexamic acid (TXA) in adolescent idiopathic scoliosis (AIS) corrective surgery.
SUMMARY OF BACKGROUND DATA: Corrective surgery for AIS is associated with significant blood loss. Evidence on the optimum TXA dose to reduce bleeding in pediatric population is scarce.
METHODS: A total of 166 AIS patients aged between 10 and 21 years, of American Society of Anesthesiologists (ASA) physical status I and II, preoperative hemoglobin >10 g/dL, platelet count >150,000 cells/L and Cobb angle of >45° scheduled for elective single-stage posterior spinal fusion (PSF) surgery by two attending surgeons were included between March 2017 and November 2018. Patients were randomized into Group A (High Dose, 30 mg/kg TXA loading dose followed by 10 mg/kg/h infusion) and Group B (Low Dose, 10 mg/kg TXA loading dose followed by 1 mg/kg/h infusion). The primary outcome was total surgical blood loss between both groups. Secondary outcomes were transfusion requirement, perioperative changes in hemoglobin and coagulation profiles, adverse events, and factors that influence total blood loss.
RESULTS: The mean total surgical blood loss between the two groups was not significant (Group A: 928.8 ± 406.1 mL [range: 348-1857 mL]; Group B: 918.1 ± 406.2 mL [range: 271-2000 mL], P = 0.865). The median duration of surgery was 120 minutes. One patient in each group received allogenic blood transfusion during the perioperative period. There were no significant changes in hemoglobin and coagulation profile at pre-operation, post-operation 0 hour and 48 hours. Sex, number of vertebral levels fused, and duration of surgery were independently associated with total surgical blood loss. No adverse events were observed perioperatively.
CONCLUSION: Low-dose TXA was as efficacious as high-dose TXA in reducing blood loss and allogenic blood transfusion for AIS patients undergoing PSF surgery.Level of Evidence: 1.
Three decades of sea water abstraction by Kapar power plant (Malaysia): What impacts on tropical zooplankton community?

Chew LL, Chong VC, Wong RCS, Lehette P, Ng CC, Loh KH

Mar Pollut Bull, 2015 Dec 15;101(1):69-84.
PMID: 26581817 DOI: 10.1016/j.marpolbul.2015.11.022

Zooplankton samples collected before (1985-86) and after (2013-14) the establishment of Kapar power station (KPS) were examined to test the hypothesis that increased sea surface temperature (SST) and other water quality changes have altered the zooplankton community structure. Elevated SST and reduced pH were detected between before and after impact pairs, with the greatest impact at the station closest to KPS. Present PAHs and heavy metal concentrations are unlikely causal factors. Water parameter changes did not affect diversity but community structure of the zooplankton. Tolerant small crustaceans, salps and larvaceans likely benefited from elevated temperature, reduced pH and shift to a more significant microbial loop exacerbated by eutrophication, while large crustaceans were more vulnerable to such changes. It is predicted that any further rise in SST will remove more large-bodied crustacean zooplankton, the preferred food for fish larvae and other meroplankton, with grave consequences to fishery production.
Fulltext Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma

Tan LP, Tan GW, Sivanesan VM, Goh SL, Ng XJ, Lim CS, et al.

Int J Cancer, 2020 04 15;146(8):2336-2347.
PMID: 31469434 DOI: 10.1002/ijc.32656

Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein-Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost-effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI-W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI-W 121 bp and ebv-miR-BART7-3p were validated. Hsa-miR-29a-3p and hsa-miR-103a-3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI-W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.
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.
Slow carbamazepine clearance in a nonadherent Malay woman with epilepsy and thyrotoxicosis

Yeap LL, Lim KS, Ng CC, Hui-Ping Khor A, Lo YL

Ther Drug Monit, 2014 Feb;36(1):3-9.
PMID: 24342894 DOI: 10.1097/FTD.0000000000000024

The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.
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
Fulltext SNP variants associated with non-Hodgkin lymphoma (NHL) correlate with human leukocyte antigen (HLA) class II expression

Ten LC, Chin YM, Tai MC, Chin EF, Lim YY, Suthandiram S, et al.

Sci Rep, 2017 01 31;7:41400.
PMID: 28139690 DOI: 10.1038/srep41400

Large consortia efforts and genome-wide association studies (GWASs) have linked a number of genetic variants within the 6p21 chromosomal region to non-Hodgkin lymphoma (NHL). Complementing these efforts, we genotyped previously reported SNPs in the human leukocyte antigen (HLA) class I (rs6457327) and class II (rs9271100, rs2647012 and rs10484561) regions in a total of 1,145 subjects (567 NHL cases and 578 healthy controls) from two major ethnic groups in Malaysia, the Malays and the Chinese. We identified a NHL-associated (PNHL_add = 0.0008; ORNHL_add = 0.54; 95% CI = 0.37-0.77) and B-cell associated (PBcell_add = 0.0007; ORBcell_add = 0.51; 95% CI = 0.35-0.76) SNP rs2647012 in the Malaysian Malays. In silico cis-eQTL analysis of rs2647012 suggests potential regulatory function of nearby HLA class II molecules. Minor allele rs2647012-T is linked to higher expression of HLA-DQB1, rendering a protective effect to NHL risk. Our findings suggest that the HLA class II region plays an important role in NHL etiology.
SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy

Roshandel D, Sanders EJ, Shakeshaft A, Panjwani N, Lin F, Collingwood A, et al.

NPJ Genom Med, 2023 Sep 28;8(1):28.
PMID: 37770509 DOI: 10.1038/s41525-023-00370-z

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.
Roles and significance of chelating agents for potentially toxic elements (PTEs) phytoremediation in soil: A review

Zulkernain NH, Uvarajan T, Ng CC

J Environ Manage, 2023 Sep 01;341:117926.
PMID: 37163837 DOI: 10.1016/j.jenvman.2023.117926

Phytoremediation is a biological remediation technique known for low-cost technology and environmentally friendly approach, which employs plants to extract, stabilise, and transform various compounds, such as potentially toxic elements (PTEs), in the soil or water. Recent developments in utilising chelating agents soil remediation have led to a renewed interest in chelate-induced phytoremediation. This review article summarises the roles of various chelating agents and the mechanisms of chelate-induced phytoremediation. This paper also discusses the recent findings on the impacts of chelating agents on PTEs uptake and plant growth and development in phytoremediation. It was found that the chelating agents have increased the rate of metal absorption and translocation up to 45% from roots to the aboveground plant parts during PTEs phytoremediation. Besides, it was also explored that the plants may experience some phytotoxicity after adding chelating agents to the soil. However, due to the leaching potential of synthetic chelating agents, the use of organic chelants have been explored to be used in PTEs phytoremediation. Finally, this paper also presents comprehensive insights on the significance of using chelating agents through SWOT analysis to discuss the advantages and limitations of chelate-induced phytoremediation.
Recombinant production of Epstein-Barr virus BZLF1 trans-activator and characterization of its DNA-binding specificity

Lim CS, Goh SL, Krishnan G, Ng CC

Protein Expr Purif, 2014 Mar;95:8-12.
PMID: 24291446 DOI: 10.1016/j.pep.2013.11.007

This paper describes the recombinant production of a biologically active Epstein-Barr virus BZLF1 trans-activator, i.e., Z-encoded broadly reactive activator (ZEBRA), that recognized specific DNA motifs. We used auto-induction for histidine-tagged BZLF1 expression in Escherichia coli and immobilized cobalt affinity membrane chromatography for protein purification under native conditions. We obtained the purified BZLF1 at a yield of 5.4mg per gram of wet weight cells at 75% purity, in which 27% of the recombinant BZLF1 remained biologically active. The recombinant BZLF1 bound to oligonucleotides containing ZEBRA response elements, either AP-1 or ZIIIB, but not a ZIIIB mutant. The recombinant BZLF1 showed a specific DNA-binding activity which could be useful for functional studies.
Fulltext R54C Mutation of NOTCH3 Gene in the First Rungus Family with CADASIL

Lim KS, Tan AH, Lim CS, Chua KH, Lee PC, Ramli N, et al.

PLoS One, 2015;10(8):e0135470.
PMID: 26270344 DOI: 10.1371/journal.pone.0135470

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary stroke caused by mutations in NOTCH3 gene. We report the first case of CADASIL in an indigenous Rungus (Kadazan-Dusun) family in Kudat, Sabah, Malaysia confirmed by a R54C (c.160C>T, p.Arg54Cys) mutation in the NOTCH3. This mutation was previously reported in a Caucasian and two Korean cases of CADASIL. We recruited two generations of the affected Rungus family (n = 9) and found a missense mutation (c.160C>T) in exon 2 of NOTCH3 in three siblings. Two of the three siblings had severe white matter abnormalities in their brain MRI (Scheltens score 33 and 50 respectively), one of whom had a young stroke at the age of 38. The remaining sibling, however, did not show any clinical features of CADASIL and had only minimal changes in her brain MRI (Scheltens score 17). This further emphasized the phenotype variability among family members with the same mutation in CADASIL. This is the first reported family with CADASIL in Rungus subtribe of Kadazan-Dusun ethnicity with a known mutation at exon 2 of NOTCH3. The penetrance of this mutation was not complete during the course of this study.
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.
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.
Potential role of regulatory DNA variants in modifying the risk of severe cutaneous reactions induced by aromatic anti-seizure medications

Mullan KA, Anderson A, Shi YW, Ding JH, Ng CC, Chen Z, et al.

Epilepsia, 2022 Feb 16.
PMID: 35170024 DOI: 10.1111/epi.17182

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions. Antiseizure medications (ASMs) with aromatic ring structure, including carbamazepine, are among the most common culprits. Screening for human leukocyte antigen (HLA) allele HLA-B*15:02 is recommended prior to initiating treatment with carbamazepine in Asians, but this allele has low positive predictive value.
METHODS: We performed whole genome sequencing and analyzed 6 199 696 common variants among 113 aromatic ASM-induced SJS/TEN cases and 84 tolerant controls of Han Chinese ethnicity.
RESULTS: In the primary analysis, nine variants reached genome-wide significance (p
Phytoassessment of Vetiver grass enhanced with EDTA soil amendment grown in single and mixed heavy metal-contaminted soil

Ng CC, Boyce AN, Abas MR, Mahmood NZ, Han F

Environ Monit Assess, 2019 Jun 14;191(7):434.
PMID: 31201562 DOI: 10.1007/s10661-019-7573-2

Over the years, ethylene-diamine-tetra-acetate (EDTA) has been widely used for many purposes. However, there are inadequate phytoassessment studies conducted using EDTA in Vetiver grass. Hence, this study evaluates the phytoassessment (growth performance, accumulation trends, and proficiency of metal uptake) of Vetiver grass, Vetiveria zizanioides (Linn.) Nash in both single and mixed heavy metal (Cd, Pb, Cu, and Zn)-disodium EDTA-enhanced contaminated soil. The plant growth, metal accumulation, and overall efficiency of metal uptake by different plant parts (lower root, upper root, lower tiller, and upper tiller) were thoroughly examined. The relative growth performance, metal tolerance, and phytoassessment of heavy metal in roots and tillers of Vetiver grass were examined. Metals in plants were measured using the flame atomic absorption spectrometry (F-AAS) after acid digestion. The root-tiller (R/T) ratio, biological concentration factor (BCF), biological accumulation coefficient (BAC), tolerance index (TI), translocation factor (TF), and metal uptake efficacy were used to estimate the potential of metal accumulation and translocation in Vetiver grass. All accumulation of heavy metals were significantly higher (p < 0.05) in both lower and upper roots and tillers of Vetiver grass for Cd + Pb + Cu + Zn + EDTA treatments as compared with the control. The single Zn + EDTA treatment accumulated the highest overall total amount of Zn (8068 ± 407 mg/kg) while the highest accumulation for Cu (1977 ± 293 mg/kg) and Pb (1096 ± 75 mg/kg) were recorded in the mixed Cd + Pb + Cu + Zn + EDTA treatment, respectively. Generally, the overall heavy metal accumulation trends of Vetiver grass were in the order of Zn > Cu > Pb > Cd for all treatments. Furthermore, both upper roots and tillers of Vetiver grass recorded high tendency of accumulation for appreciably greater amounts of all heavy metals, regardless of single and/or mixed metal treatments. Thus, Vetiver grass can be recommended as a potential phytoextractor for all types of heavy metals, whereby its tillers will act as the sink for heavy metal accumulation in the presence of EDTA for all treatments.

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