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  1. Fulltext Prevalence of pharmacogenomic variants in 100 pharmacogenes among Southeast Asian populations under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm)
    Runcharoen C, Fukunaga K, Sensorn I, Iemwimangsa N, Klumsathian S, Tong H, et al.
    Hum Genome Var, 2021 Feb 04;8(1):7.
    PMID: 33542200 DOI: 10.1038/s41439-021-00135-z
    Pharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.
  2. Southeast Asian Pharmacogenomics Research Network (SEAPharm): Current Status and Perspectives
    Chumnumwat S, Lu ZH, Sukasem C, Winther MD, Capule FR, Abdul Hamid AAAT, et al.
    Public Health Genomics, 2019;22(3-4):132-139.
    PMID: 31587001 DOI: 10.1159/000502916
    Pharmacogenomics (PGx) is increasingly being recognized as a potential tool for improving the efficacy and safety of drug therapy. Therefore, several efforts have been undertaken globally to facilitate the implementation process of PGx into routine clinical practice. Part of these efforts include the formation of PGx working groups working on PGx research, synthesis, and dissemination of PGx data and creation of PGx implementation strategies. In Asia, the Southeast Asian Pharmacogenomics Research Network (SEAPharm) is established to enable and strengthen PGx research among the various PGx communities within but not limited to countries in SEA; with the ultimate goal to support PGx implementation in the region. From the perspective of SEAPharm member countries, there are several key elements essential for PGx implementation at the national level. They include pharmacovigilance database, PGx research, health economics research, dedicated laboratory to support PGx testing for both research and clinical use, structured PGx education, and supportive national health policy. The status of these essential elements is presented here to provide a broad picture of the readiness for PGx implementation among the SEAPharm member countries, and to strengthen the PGx research network and practice in this region.
  3. Construction of a microRNA-mRNA Regulatory Network in De Novo Cytogenetically Normal Acute Myeloid Leukemia Patients
    Esa E, Hashim AK, Mohamed EHM, Zakaria Z, Abu Hassan AN, Mat Yusoff Y, et al.
    Genet Test Mol Biomarkers, 2021 Mar;25(3):199-210.
    PMID: 33734890 DOI: 10.1089/gtmb.2020.0182
    Background: The association between dysregulated microRNAs (miRNAs) and acute myeloid leukemia (AML) is well known. However, our understanding of the regulatory role of miRNAs in the cytogenetically normal AML (CN-AML) subtype pathway is still poor. The current study integrated miRNA and mRNA profiles to explore novel miRNA-mRNA interactions that affect the regulatory patterns of de novo CN-AML. Methods: We utilized a multiplexed nanoString nCounter platform to profile both miRNAs and mRNAs using similar sets of patient samples (n = 24). Correlations were assessed, and an miRNA-mRNA network was constructed. The underlying biological functions of the mRNAs were predicted by gene enrichment. Finally, the interacting pairs were assessed using TargetScan and microT-CDS. We identified 637 significant negative correlations (false discovery rate <0.05). Results: Network analysis revealed a cluster of 12 miRNAs representing the majority of mRNA targets. Within the cluster, five miRNAs (miR-495-3p, miR-185-5p, let-7i-5p, miR-409-3p, and miR-127-3p) were posited to play a pivotal role in the regulation of CN-AML, as they are associated with the negative regulation of myeloid leukocyte differentiation, negative regulation of myeloid cell differentiation, and positive regulation of hematopoiesis. Conclusion: Three novel interactions in CN-AML were predicted as let-7i-5p:HOXA9, miR-495-3p:PIK3R1, and miR-495-3p:CDK6 may be responsible for regulating myeloid cell differentiation in CN-AML.
  4. Fulltext Genome-wide analysis of copy number variation identifies candidate gene loci associated with the progression of non-alcoholic fatty liver disease
    Zain SM, Mohamed R, Cooper DN, Razali R, Rampal S, Mahadeva S, et al.
    PLoS One, 2014;9(4):e95604.
    PMID: 24743702 DOI: 10.1371/journal.pone.0095604
    Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD) develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC). To investigate the molecular basis of disease progression, we performed a genome-wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD [10 simple steatosis and 39 non-alcoholic steatohepatitis (NASH)] and 49 matched controls using high-density comparative genomic hybridization (CGH) microarrays. A total of 11 CNVs were found to be unique to individuals with simple steatosis, whilst 22 were common between simple steatosis and NASH, and 224 were unique to NASH. We postulated that these CNVs could be involved in the pathogenesis of NAFLD progression. After stringent filtering, we identified four rare and/or novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs, located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (XPO4) and phosphodiesterase 1B (PDE1B) genes which are already known to be involved in the etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at these four CNV loci with genes already known to be associated with NAFLD yielded a set of genes associated with shared biological processes including cell death, the key process involved in 'second hit' hepatic injury. To our knowledge, this pilot study is the first to provide CNV information of potential relevance to the NAFLD spectrum. These data could prove invaluable in predicting patients at risk of developing NAFLD and more importantly, those who will subsequently progress to NASH.
  5. Fulltext Genetic polymorphisms in LDLR, APOB, PCSK9 and other lipid related genes associated with familial hypercholesterolemia in Malaysia
    Lye SH, Chahil JK, Bagali P, Alex L, Vadivelu J, Ahmad WA, et al.
    PLoS One, 2013;8(4):e60729.
    PMID: 23593297 DOI: 10.1371/journal.pone.0060729
    Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevations in total cholesterol (TC) and low density lipoprotein cholesterol (LDLc). Development of FH can result in the increase of risk for premature cardiovascular diseases (CVD). FH is primarily caused by genetic variations in Low Density Lipoprotein Receptor (LDLR), Apolipoprotein B (APOB) or Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) genes. Although FH has been extensively studied in the Caucasian population, there are limited reports of FH mutations in the Asian population. We investigated the association of previously reported genetic variants that are involved in lipid regulation in our study cohort. A total of 1536 polymorphisms previously implicated in FH were evaluated in 141 consecutive patients with clinical FH (defined by the Dutch Lipid Clinic Network criteria) and 111 unrelated control subjects without FH using high throughput microarray genotyping platform. Fourteen Single Nucleotide Polymorphisms (SNPs) were found to be significantly associated with FH, eleven with increased FH risk and three with decreased FH risk. Of the eleven SNPs associated with an increased risk of FH, only one SNP was found in the LDLR gene, seven in the APOB gene and three in the PCSK9 gene. SNP rs12720762 in APOB gene is associated with the highest risk of FH (odds ratio 14.78, p<0.001). Amongst the FH cases, 108 out of 141 (76.60%) have had at least one significant risk-associated SNP. Our study adds new information and knowledge on the genetic polymorphisms amongst Asians with FH, which may serve as potential markers in risk prediction and disease management.
  6. Support vector machines for oil classification link with polyaromatic hydrocarbon contamination in the environment
    Ismail A, Juahir H, Mohamed SB, Toriman ME, Kassim AM, Zain SM, et al.
    Water Sci Technol, 2021 Mar;83(5):1039-1054.
    PMID: 33724935 DOI: 10.2166/wst.2021.038
    The main focus of this study is exploring the spatial distribution of polyaromatics hydrocarbon links between oil spills in the environment via Support Vector Machines based on Kernel-Radial Basis Function (RBF) approach for high precision classification of oil spill type from its sample fingerprinting in Peninsular Malaysia. The results show the highest concentrations of Σ Alkylated PAHs and Σ EPA PAHs in ΣTAH concentration in diesel from the oil samples PP3_liquid and GP6_Jetty achieving 100% classification output, corresponding to coherent decision boundary and projective subspace estimation. The high dimensional nature of this approach has led to the existence of a perfect separability of the oil type classification from four clustered oil type components; i.e diesel, bunker C, Mixture Oil (MO), lube oil and Waste Oil (WO) with the slack variables of ξ ≠ 0. Of the four clusters, only the SVs of two are correctly predicted, namely diesel and MO. The kernel-RBF approach provides efficient and reliable oil sample classification, enabling the oil classification to be optimally performed within a relatively short period of execution and a faster dataset classification where the slack variables ξ are non-zero.
  7. Chemometric techniques in oil classification from oil spill fingerprinting
    Ismail A, Toriman ME, Juahir H, Kassim AM, Zain SM, Ahmad WKW, et al.
    Mar Pollut Bull, 2016 Oct 15;111(1-2):339-346.
    PMID: 27397593 DOI: 10.1016/j.marpolbul.2016.06.089
    Extended use of GC-FID and GC-MS in oil spill fingerprinting and matching is significantly important for oil classification from the oil spill sources collected from various areas of Peninsular Malaysia and Sabah (East Malaysia). Oil spill fingerprinting from GC-FID and GC-MS coupled with chemometric techniques (discriminant analysis and principal component analysis) is used as a diagnostic tool to classify the types of oil polluting the water. Clustering and discrimination of oil spill compounds in the water from the actual site of oil spill events are divided into four groups viz. diesel, Heavy Fuel Oil (HFO), Mixture Oil containing Light Fuel Oil (MOLFO) and Waste Oil (WO) according to the similarity of their intrinsic chemical properties. Principal component analysis (PCA) demonstrates that diesel, HFO, MOLFO and WO are types of oil or oil products from complex oil mixtures with a total variance of 85.34% and are identified with various anthropogenic activities related to either intentional releasing of oil or accidental discharge of oil into the environment. Our results show that the use of chemometric techniques is significant in providing independent validation for classifying the types of spilled oil in the investigation of oil spill pollution in Malaysia. This, in consequence would result in cost and time saving in identification of the oil spill sources.
  8. Improving oil classification quality from oil spill fingerprint beyond six sigma approach
    Juahir H, Ismail A, Mohamed SB, Toriman ME, Kassim AM, Zain SM, et al.
    Mar Pollut Bull, 2017 Jul 15;120(1-2):322-332.
    PMID: 28535957 DOI: 10.1016/j.marpolbul.2017.04.032
    This study involves the use of quality engineering in oil spill classification based on oil spill fingerprinting from GC-FID and GC-MS employing the six-sigma approach. The oil spills are recovered from various water areas of Peninsular Malaysia and Sabah (East Malaysia). The study approach used six sigma methodologies that effectively serve as the problem solving in oil classification extracted from the complex mixtures of oil spilled dataset. The analysis of six sigma link with the quality engineering improved the organizational performance to achieve its objectivity of the environmental forensics. The study reveals that oil spills are discriminated into four groups' viz. diesel, hydrocarbon fuel oil (HFO), mixture oil lubricant and fuel oil (MOLFO) and waste oil (WO) according to the similarity of the intrinsic chemical properties. Through the validation, it confirmed that four discriminant component, diesel, hydrocarbon fuel oil (HFO), mixture oil lubricant and fuel oil (MOLFO) and waste oil (WO) dominate the oil types with a total variance of 99.51% with ANOVA giving Fstat>Fcritical at 95% confidence level and a Chi Square goodness test of 74.87. Results obtained from this study reveals that by employing six-sigma approach in a data-driven problem such as in the case of oil spill classification, good decision making can be expedited.
  9. Intracellular and exosomal microRNAome profiling of human vascular smooth muscle cells during replicative senescence
    Nguyen DDN, Zain SM, Kamarulzaman MH, Low TY, Chilian WM, Pan Y, et al.
    Am J Physiol Heart Circ Physiol, 2021 10 01;321(4):H770-H783.
    PMID: 34506226 DOI: 10.1152/ajpheart.00058.2021
    Vascular aging is highly associated with cardiovascular morbidity and mortality. Although the senescence of vascular smooth muscle cells (VSMCs) has been well established as a major contributor to vascular aging, intracellular and exosomal microRNA (miRNA) signaling pathways in senescent VSMCs have not been fully elucidated. This study aimed to identify the differential expression of intracellular and exosomal miRNA in human VSMCs (hVSMCs) during replicative senescence. To achieve this aim, intracellular and exosomal miRNAs were isolated from hVSMCs and subsequently subjected to whole genome small RNA next-generation sequencing, bioinformatics analyses, and qPCR validation. Three significant findings were obtained. First, senescent hVSMC-derived exosomes tended to cluster together during replicative senescence and the molecular weight of the exosomal protein tumor susceptibility gene 101 (TSG-101) increased relative to the intracellular TSG-101, suggesting potential posttranslational modifications of exosomal TSG-101. Second, there was a significant decrease in both intracellular and exosomal hsa-miR-155-5p expression [n = 3, false discovery rate (FDR) < 0.05], potentially being a cell type-specific biomarker of hVSMCs during replicative senescence. Importantly, hsa-miR-155-5p was found to associate with cell-cycle arrest and elevated oxidative stress. Lastly, miRNAs from the intracellular pool, that is, hsa-miR-664a-3p, hsa-miR-664a-5p, hsa-miR-664b-3p, hsa-miR-4485-3p, hsa-miR-10527-5p, and hsa-miR-12136, and that from the exosomal pool, that is, hsa-miR-7704, were upregulated in hVSMCs during replicative senescence (n = 3, FDR < 0.05). Interestingly, these novel upregulated miRNAs were not functionally well annotated in hVSMCs to date. In conclusion, hVSMC-specific miRNA expression profiles during replicative senescence potentially provide valuable insights into the signaling pathways leading to vascular aging.NEW & NOTEWORTHY This is the first study on intracellular and exosomal miRNA profiling on human vascular smooth muscle cells during replicative senescence. Specific dysregulated sets of miRNAs were identified from human vascular smooth muscle cells. Hsa-miR-155-5p was significantly downregulated in both intracellular and exosomal hVSMCs, suggesting its crucial role in cellular senescence. Hsa-miR-155-5p might be the mediator in linking cellular senescence to vascular aging and atherosclerosis.
  10. Fulltext Effect of polymorphisms within methotrexate pathway genes on methotrexate toxicity and plasma levels in adults with hematological malignancies
    Suthandiram S, Gan GG, Zain SM, Bee PC, Lian LH, Chang KM, et al.
    Pharmacogenomics, 2014 Aug;15(11):1479-94.
    PMID: 25303299 DOI: 10.2217/pgs.14.97
    Pharmacogenetics of methotrexate (MTX) contributes to interindividual differences in toxicity. We aimed to evaluate the impact of SNPs within the MTX pathway genes on MTX-induced toxicity and MTX plasma levels at 48 h following treatment in Asian adults with acute lymphoblastic leukemia or non-Hodgkin lymphoma.
  11. Rational design of carbonitrile-carboxaldehyde cation receptor models: probing the nature of the heteroatom-metal interaction
    Rosli AN, Abu Bakar MA, Lee VS, Zain SM, Ahmad MR, Abdul Manan NS, et al.
    J Mol Model, 2014 Sep;20(9):2428.
    PMID: 25149440 DOI: 10.1007/s00894-014-2428-9
    In this work, hybrid functional and G4 methods were employed in the rational design of carbonitrile-carboxaldehyde receptor models for cation recognition. Electron-sharing and ionic interactions between the models and the cations were analyzed utilizing the concepts of overlap population, atomic valence, electrostatic potential, and CHELPG charge in order to elucidate the nature of the heteroatom-metal interaction, the N versus O disparity, and the effect of pH. Receptor fragment models from ionomycin were employed to rationalize the selection of receptor models for discriminating group I cations and enhancing the selectivity for Mg(II) rather than Ca(II), and to examine the effects of keto-enol forms and negatively charged sites. The changes in geometries, overlap population, metal valence, and CHELPG charge upon solvation in heptane medium as compared to the gas phase were negligible. The optimized geometries reveal that the interaction between group II cations and the keto, enol, and enolate forms of 2-cyanoethanal causes 12 % bending of the C-C-N angle from linearity. Overlap populations show that the electron-sharing interaction favors group II cations but that the same mechanism allows Li(I) to compete. The total spin of Li(I) is 17 % greater than that of Ca(II), but the G4 binding energies of the two are separated by more than 50 kcal/mol, favoring group II cations, which may eliminate interference from Li(I). 1,2-Dicyanoethylene, which has only one form, shows similar characteristics. CHELPG analysis shows that Mg(II) transfers 25 and 18 % of its positive charge to 2-cyanoethanal enolate and 1,2-dicyanoethylene, respectively. Hydrogen atoms receive most of the positive charge in both receptors, but the N-termini exhibit strikingly different characteristics. Electrostatic potential contour profiles were found to be in good agreement with the atomic charge distributions. The application of uncharged 1,3-dicarbonyl and 2-cyanocarbonyl receptors and a judicious choice of polymeric membrane that suppresses the Hofmeister effect should lead to high selectivity for magnesium, whereas the utilization of multiple negatively charged ionophores should result in selectivity for calcium.
  12. Polymorphisms in methylenetetrahydrofolate reductase gene and risk of non-Hodgkin lymphoma in a multi-ethnic population
    Suthandiram S, Gan GG, Zain SM, Haerian BS, Bee PC, Lian LH, et al.
    J Hum Genet, 2014 May;59(5):280-7.
    PMID: 24646728 DOI: 10.1038/jhg.2014.19
    An imbalance in folate metabolism can adversely affect DNA synthesis and methylation systems which can lead to susceptibility to non-Hodgkin lymphoma (NHL). Whether single nucleotide polymorphisms (SNPs) and their haplotypes in the methylenetetrahydrofolate reductase (MTHFR) are associated with NHL, remain inconclusive. We investigated the association between MTHFR C677T and A1298C SNPs and NHL risk in a population which is made up of Malay, Chinese and Indian ethnic subgroups. A total of 372 NHL patients and 722 controls were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects failed to demonstrate significant association between the MTHFR C677T and A1298C SNPs with NHL and its subtypes. The results were in agreement with the previous meta-analyses. In the Indian ethnic subgroup however, single locus analysis of MTHFR A1298C appears to confer risk to NHL (Odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.22-3.00, P=0.006). The risk is almost doubled in homozygous carrier of MTHFR 1298CC (OR 4.03, 95% CI 1.56-10.43, P=0.004). Haplotype analysis revealed higher frequency of CC in the Indian NHL patients compared with controls (OR 1.86, 95% CI 1.18-2.93, P=0.007). There is lack of evidence to suggest an association between MTHFR C677T and A1298C with the risk of NHL in the Malays and Chinese. In the Indians however, the MTHFR A1298C confers risk to NHL. This study suggests ethnicity modifies the relationship between polymorphisms in the folate-metabolizing gene and NHL.
  13. Spatial and temporal air quality pattern recognition using environmetric techniques: a case study in Malaysia
    Syed Abdul Mutalib SN, Juahir H, Azid A, Mohd Sharif S, Latif MT, Aris AZ, et al.
    Environ Sci Process Impacts, 2013 Sep;15(9):1717-28.
    PMID: 23831918 DOI: 10.1039/c3em00161j
    The objective of this study is to identify spatial and temporal patterns in the air quality at three selected Malaysian air monitoring stations based on an eleven-year database (January 2000-December 2010). Four statistical methods, Discriminant Analysis (DA), Hierarchical Agglomerative Cluster Analysis (HACA), Principal Component Analysis (PCA) and Artificial Neural Networks (ANNs), were selected to analyze the datasets of five air quality parameters, namely: SO2, NO2, O3, CO and particulate matter with a diameter size of below 10 μm (PM10). The three selected air monitoring stations share the characteristic of being located in highly urbanized areas and are surrounded by a number of industries. The DA results show that spatial characterizations allow successful discrimination between the three stations, while HACA shows the temporal pattern from the monthly and yearly factor analysis which correlates with severe haze episodes that have happened in this country at certain periods of time. The PCA results show that the major source of air pollution is mostly due to the combustion of fossil fuel in motor vehicles and industrial activities. The spatial pattern recognition (S-ANN) results show a better prediction performance in discriminating between the regions, with an excellent percentage of correct classification compared to DA. This study presents the necessity and usefulness of environmetric techniques for the interpretation of large datasets aiming to obtain better information about air quality patterns based on spatial and temporal characterizations at the selected air monitoring stations.
  14. Fulltext G3 assisted rational design of chemical sensor array using carbonitrile neutral receptors
    Rosli AN, Bakar MA, Manan NS, Woi PM, Lee VS, Zain SM, et al.
    Sensors (Basel), 2013;13(10):13835-60.
    PMID: 24129020 DOI: 10.3390/s131013835
    Combined computational and experimental strategies for the systematic design of chemical sensor arrays using carbonitrile neutral receptors are presented. Binding energies of acetonitrile, n-pentylcarbonitrile and malononitrile with Ca(II), Mg(II), Be(II) and H⁺ have been investigated with the B3LYP, G3, CBS-QB3, G4 and MQZVP methods, showing a general trend H⁺ > Be(II) > Mg(II) > Ca(II). Hydrogen bonding, donor-acceptor and cation-lone pair electron simple models were employed in evaluating the performance of computational methods. Mg(II) is bound to acetonitrile in water by 12.5 kcal/mol, and in the gas phase the receptor is more strongly bound by 33.3 kcal/mol to Mg(II) compared to Ca(II). Interaction of bound cations with carbonitrile reduces the energies of the MOs involved in the proposed σ-p conjugated network. The planar malononitrile-Be(II) complex possibly involves a π-network with a cationic methylene carbon. Fabricated potentiometric chemical sensors show distinct signal patterns that can be exploited in sensor array applications.
  15. Impact of leptin receptor gene variants on risk of non-alcoholic fatty liver disease and its interaction with adiponutrin gene
    Zain SM, Mohamed Z, Mahadeva S, Cheah PL, Rampal S, Chin KF, et al.
    J Gastroenterol Hepatol, 2013 May;28(5):873-9.
    PMID: 23278404 DOI: 10.1111/jgh.12104
    Genetic polymorphism has been implicated as a factor for the occurrence of non-alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD.
  16. Fulltext Copy number variation in exportin-4 (XPO4) gene and its association with histological severity of non-alcoholic fatty liver disease
    Zain SM, Mohamed Z, Pirmohamed M, Tan HL, Alshawsh MA, Mahadeva S, et al.
    Sci Rep, 2015 Aug 21;5:13306.
    PMID: 26293807 DOI: 10.1038/srep13306
    A recent genome-wide copy number (CNV) scan identified a 13q12.11 duplication in the exportin-4 (XPO4) gene to be associated with non-alcoholic steatohepatitis (NASH). We sought to confirm the finding in a larger cohort and to assess the serum XPO4 pattern in a broad spectrum of non-alcoholic fatty liver disease (NAFLD) cases. We analysed 249 NAFLD patients and 232 matched controls using TaqMan assay and serum XPO4 was measured. Copy number distribution was as follows: copy number neutral (NAFLD: 53.8%, controls: 68.6%), copy number losses (NAFLD: 13.3%, controls: 12.9%), copy number gains (NAFLD: 32.9%, controls: 18.5%). CNV gain was significantly associated with a greater risk of NAFLD (adjusted OR 2.22, 95% CI 1.42-3.46, P = 0.0004) and NASH (adjusted OR 2.33, 95% CI 1.47-3.68, P = 0.0003). Interestingly, subjects carrying extra copy number showed significantly higher serum ALT and triglyceride (P 
  17. Spatial assessment and source identification of heavy metals pollution in surface water using several chemometric techniques
    Ismail A, Toriman ME, Juahir H, Zain SM, Habir NL, Retnam A, et al.
    Mar Pollut Bull, 2016 May 15;106(1-2):292-300.
    PMID: 27001716 DOI: 10.1016/j.marpolbul.2015.10.019
    This study presents the determination of the spatial variation and source identification of heavy metal pollution in surface water along the Straits of Malacca using several chemometric techniques. Clustering and discrimination of heavy metal compounds in surface water into two groups (northern and southern regions) are observed according to level of concentrations via the application of chemometric techniques. Principal component analysis (PCA) demonstrates that Cu and Cr dominate the source apportionment in northern region with a total variance of 57.62% and is identified with mining and shipping activities. These are the major contamination contributors in the Straits. Land-based pollution originating from vehicular emission with a total variance of 59.43% is attributed to the high level of Pb concentration in the southern region. The results revealed that one state representing each cluster (northern and southern regions) is significant as the main location for investigating heavy metal concentration in the Straits of Malacca which would save monitoring cost and time.

    CAPSULE: The monitoring of spatial variation and source of heavy metals pollution at the northern and southern regions of the Straits of Malacca, Malaysia, using chemometric analysis.

  18. Reductive alkylation of lipase: experimental and molecular modeling approaches
    Rahman RN, Tejo BA, Basri M, Rahman MB, Khan F, Zain SM, et al.
    Appl Biochem Biotechnol, 2004 8 12;118(1-3):11-20.
    PMID: 15304735
    Candida rugosa lipase was modified via reductive alkylation to increase its hydrophobicity to work better in organic solvents. The free amino group of lysines was alkylated using propionaldehyde with different degrees of modification obtained (49 and 86%). Far-ultraviolet circular dichroism (CD) spectroscopy of the lipase in aqueous solvent showed that such chemical modifications at the enzyme surface caused a loss in secondary and tertiary structure that is attributed to the enzyme unfolding. Using molecular modeling, we propose that in an aqueous environment the loss in protein structure of the modified lipase is owing to disruption of stabilizing salt bridges, particularly of surface lysines. Indeed, molecular modeling and simulation of a salt bridge formed by Lys-75 to Asp-79, in a nonpolar environment, suggests the adoption of a more flexible alkylated lysine that may explain higher lipase activity in organic solvents on alkylation.
  19. Genetic association of LMAN2L gene in schizophrenia and bipolar disorder and its interaction with ANK3 gene polymorphism
    Lim CH, Zain SM, Reynolds GP, Zain MA, Roffeei SN, Zainal NZ, et al.
    Prog Neuropsychopharmacol Biol Psychiatry, 2014 Oct 3;54:157-62.
    PMID: 24914473 DOI: 10.1016/j.pnpbp.2014.05.017
    Recent studies have shown that bipolar disorder (BPD) and schizophrenia (SZ) share some common genetic risk factors. This study aimed to examine the association between candidate single nucleotide polymorphisms (SNPs) identified from genome-wide association studies (GWAS) and risk of BPD and SZ. A total of 715 patients (244 BPD and 471 SZ) and 593 controls were genotyped using the Sequenom MassARRAY platform. We showed a positive association between LMAN2L (rs6746896) and risk of both BPD and SZ in a pooled population (P-value=0.001 and 0.009, respectively). Following stratification by ethnicity, variants of the ANK3 gene (rs1938516 and rs10994336) were found to be associated with BPD in Malays (P-value=0.001 and 0.006, respectively). Furthermore, an association exists between another variant of LMAN2L (rs2271893) and SZ in the Malay and Indian ethnic groups (P-value=0.003 and 0.002, respectively). Gene-gene interaction analysis revealed a significant interaction between the ANK3 and LMAN2L genes (empirical P=0.0107). Significant differences were shown between patients and controls for two haplotype frequencies of LMAN2L: GA (P=0.015 and P=0.010, for BPD and SZ, respectively) and GG (P=0.013 for BPD). Our study showed a significant association between LMAN2L and risk of both BPD and SZ.
  20. Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene
    Tan HL, Zain SM, Mohamed R, Rampal S, Chin KF, Basu RC, et al.
    J Gastroenterol, 2014 Jun;49(6):1056-64.
    PMID: 23800943 DOI: 10.1007/s00535-013-0850-x
    BACKGROUND: Recent genome-wide association studies demonstrated an association between single nucleotide polymorphisms (SNPs) on the glucokinase regulatory gene (GCKR) with hepatic steatosis. This study attempted to investigate the association of GCKR rs780094 and rs1260326 with susceptibility to non-alcoholic fatty liver disease (NAFLD) and its severity.

    METHODS: The genotypes were assessed on 144 histologically confirmed NAFLD patients and 198 controls using a Sequenom MassARRAY platform.

    RESULTS: The GCKR rs1260326 and rs780094 allele T were associated with susceptibility to NAFLD (OR 1.49, 95 % CI 1.09-2.05, p = 0.012; and OR 1.51, 95 % CI 1.09-2.09, p = 0.013, respectively), non-alcoholic steatohepatitis (NASH) (OR 1.55, 95 % CI 1.10-2.17, p = 0.013; and OR 1.56, 95 % CI 1.10-2.20, p = 0.012, respectively) and NASH with significant fibrosis (OR 1.50, 95 % CI 1.01-2.21, p = 0.044; and OR 1.52, 95 % CI 1.03-2.26, p = 0.038, respectively). Following stratification by ethnicity, significant association was seen in Indian patients between the two SNPs and susceptibility to NAFLD (OR 2.64, 95 % CI 1.28-5.43, p = 0.009; and OR 4.35, 95 % CI 1.93-9.81, p < 0.0001, respectively). The joint effect of GCKR with adiponutrin rs738409 indicated greatly increased the risk of NAFLD (OR 4.14, 95 % CI 1.41-12.18, p = 0.010). Histological data showed significant association of GCKR rs1260326 with high steatosis grade (OR 1.76, 95 % CI 1.08-2.85, p = 0.04).

    CONCLUSION: This study suggests that risk allele T of the GCKR rs780094 and rs1260326 is associated with predisposition to NAFLD and NASH with significant fibrosis. The GCKR and PNPLA3 genes interact to result in increased susceptibility to NAFLD.

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