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  1. Chew DCH, Khoo XH, Lee TS, Chin KY, Raja Ali RA, Muhammad Nawawi KN, et al.
    Inflamm Bowel Dis, 2024 Sep 03;30(9):1566-1578.
    PMID: 37935628 DOI: 10.1093/ibd/izad189
    The incidence of inflammatory bowel disease (IBD) has been increasing in Southeast Asia (SEA) in tandem with its economic growth and urbanization over the past 2 decades. Specific characteristics of IBD in SEA are similar to East Asia and the West, such as the declining ratio of ulcerative colitis to Crohn's disease. However, exceptionally low familial aggregation is seen. Smoking is also not a common risk factor in patients with Crohn's disease. The incidence of perianal disease is higher in SEA than in Australia and is comparable to the West. In a multiracial population, such as Singapore and Malaysia, Indians have the highest incidence and prevalence rates, which are likely to be due to important putative mutations. For instance, a higher frequency of the NOD2 predisposing mutation SNP5 and IBD risk allele IGR2198a and IGR2092a were found in Indians. Although differences in the genetic constitution play an important role in the epidemiology and prognosis of IBD in SEA, the emergence of this disease offers a unique opportunity to identify potential exposomes that contribute to its pathogenesis.
    Matched MeSH terms: Genetic Predisposition to Disease
  2. Ng JS, Hamilton DG
    J Med Screen, 2022 Dec;29(4):209-218.
    PMID: 35593115 DOI: 10.1177/09691413221101807
    OBJECTIVE: The ongoing COVID-19 pandemic has caused an indefinite delay to cancer screening programs worldwide. This study aims to explore the impact on breast cancer screening outcomes such as mammography and diagnosis rates.

    METHODS: We searched Ovid MEDLINE, Ovid Embase, medRxiv and bioRxiv between January 2020 to October 2021 to identify studies that reported on the rates of screening mammography and breast cancer diagnosis before and during the pandemic. The effects of 'lockdown' measures, age and ethnicity on outcomes were also examined. All studies were assessed for risk of bias using the Newcastle-Ottawa Scale (NOS). Rate ratios were calculated for all outcomes and pooled using standard inverse-variance random effects meta-analysis.

    RESULTS: We identified 994 articles, of which 7 registry-based and 24 non-registry-based retrospective cohort studies, including data on 4,860,786 and 629,823 patients respectively across 18 different countries, were identified. Overall, breast cancer screening and diagnosis rates dropped by an estimated 41-53% and 18-29% respectively between 2019 and 2020. No differences in mammogram screening rates depending on patient age or ethnicity were observed. However, countries that implemented lockdown measures were associated with a significantly greater reduction in mammogram and diagnosis rates between 2019 and 2020 in comparison to those that did not.

    CONCLUSION: The pandemic has caused a substantial reduction in the screening and diagnosis of breast cancer, with reductions more pronounced in countries under lockdown restrictions. It is early yet to know if delayed screening during the pandemic translates into higher breast cancer mortality.

    Matched MeSH terms: Communicable Disease Control
  3. Aldoghachi AF, Yanagisawa D, Pahrudin Arrozi A, Abu Bakar ZH, Taguchi H, Ishigaki S, et al.
    Biochem Biophys Res Commun, 2024 Jan 29;694:149392.
    PMID: 38142581 DOI: 10.1016/j.bbrc.2023.149392
    Thioredoxin interacting protein (TXNIP) has emerged as a significant regulator of β-cell mass and loss, rendering it an attractive target for treating diabetes. We previously showed that Shiga-Y6, a fluorinated curcumin derivative, inhibited TXNIP mRNA and protein expression in vitro, raising the question of whether the same effect could be translated in vivo. Herein, we examined the effect of Shiga-Y6 on TNXIP levels and explored its therapeutic potential in a mouse model of diabetes, Akita mice. We intraperitoneally injected Shiga-Y6 (SY6; 30 mg/kg of body weight) or vehicle into 8-week-old Akita mice for 28 consecutive days. On day 29, the mice were euthanized, following which the serum levels of glucose, insulin, and glucagon were measured using ELISA, the expression of TXNIP in pancreatic tissue lysates was determined using western blotting, and the level of β-cell apoptosis was assessed using the TUNEL assay. TXNIP levels in the pancreatic tissue of Akita mice were significantly elevated compared with wild-type (WT) mice. Shiga-Y6 administration for 28 days significantly lowered those levels compared with Akita mice that received vehicle to a level comparable to WT mice. In immunohistochemical analysis, both α- to β-cell ratio and the number of apoptotic β-cells were significantly reduced in SY6-treated Akita mice, compared with vehicle-treated Akita mice. Findings from the present study suggest a potential of Shiga-Y6 as an antidiabetic agent through lowering TXNIP protein levels and ameliorating pancreatic β-cells apoptosis.
    Matched MeSH terms: Disease Models, Animal
  4. Au A, Griffiths LR, Cheng KK, Wee Kooi C, Irene L, Keat Wei L
    Sci Rep, 2015 Dec 15;5:18224.
    PMID: 26666837 DOI: 10.1038/srep18224
    Both OLR1 and PCSK9 genes are associated with atherosclerosis, cardiovascular disease and ischemic stroke. The overall prevalence of PCSK9 rs505151 and OLR1 rs11053646 variants in ischemic stroke were 0.005 and 0.116, respectively. However, to date, association between these polymorphisms and ischemic stroke remains inconclusive. Therefore, this first meta-analysis was carried out to clarify the presumed influence of these polymorphisms on ischemic stroke. All eligible case-control and cohort studies that met the search terms were retrieved in multiple databases. Demographic and genotyping data were extracted from each study, and the meta-analysis was performed using RevMan 5.3 and Metafor R 3.2.1. The pooled odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed- and random-effect models. Seven case-control studies encompassing 1897 cases and 2119 controls were critically evaluated. Pooled results from the genetic models indicated that OLR1 rs11053646 dominant (OR = 1.33, 95%  CI:1.11-1.58) and co-dominant models (OR = 1.24, 95%  CI:1.02-1.51) were significantly associated with ischemic stroke. For the PCSK9 rs505151 polymorphism, the OR of co-dominant model (OR = 1.36, 95%  CI:1.01-1.58) was found to be higher among ischemic stroke patients. In conclusion, the current meta-analysis highlighted that variant allele of OLR1 rs11053646 G > C and PCSK9 rs505151 A > G may contribute to the susceptibility risk of ischemic stroke.
    Matched MeSH terms: Genetic Predisposition to Disease*
  5. Thong KS, Chee KY, Ng CG, Walterfang M, Velakoulis D
    Asia Pac Psychiatry, 2016 Sep;8(3):238-40.
    PMID: 26615809 DOI: 10.1111/appy.12227
    This study aims to establish psychometric properties of the Malay Neuropsychiatry Unit Cognitive Assessment Tool (Malay NuCOG) in Alzheimer's disease. NuCOG was translated to Malay language and compared with Montreal Cognitive Assessment Tool on 80 individuals. The Malay NuCOG showed good internal consistency and reliability (Cronbach's alpha = 0.895). It demonstrated 100% sensitivity and 87.5% specificity at the cutoff score of 78.50/100. The Malay NuCOG is a valid and reliable cognitive instrument that is sensitive and specific for the detection of dementia and has clinical advantages in its ability to examine individual cognitive domains.
    Matched MeSH terms: Alzheimer Disease/diagnosis*
  6. Haridan US, Mokhtar U, Machado LR, Abdul Aziz AT, Shueb RH, Zaid M, et al.
    PLoS One, 2015;10(1):e0116791.
    PMID: 25594501 DOI: 10.1371/journal.pone.0116791
    The FCGR3 locus encoding the low affinity activating receptor FcγRIII, plays a vital role in immunity triggered by cellular effector and regulatory functions. Copy number of the genes FCGR3A and FCGR3B has previously been reported to affect susceptibility to several autoimmune diseases and chronic inflammatory conditions. However, such genetic association studies often yield inconsistent results; hence require assays that are robust with low error rate. We investigated the accuracy and efficiency in estimating FCGR3 CNV by comparing Sequenom MassARRAY and paralogue ratio test-restriction enzyme digest variant ratio (PRT-REDVR). In addition, since many genetic association studies of FCGR3B CNV were carried out using real-time quantitative PCR, we have also included the evaluation of that method's performance in estimating the multi-allelic CNV of FCGR3B. The qPCR assay exhibited a considerably broader distribution of signal intensity, potentially introducing error in estimation of copy number and higher false positive rates. Both Sequenom and PRT-REDVR showed lesser systematic bias, but Sequenom skewed towards copy number normal (CN = 2). The discrepancy between Sequenom and PRT-REDVR might be attributed either to batch effects noise in individual measurements. Our study suggests that PRT-REDVR is more robust and accurate in genotyping the CNV of FCGR3, but highlights the needs of multiple independent assays for extensive validation when performing a genetic association study with multi-allelic CNVs.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  7. Johnston SC, Briese T, Bell TM, Pratt WD, Shamblin JD, Esham HL, et al.
    PLoS One, 2015;10(2):e0117817.
    PMID: 25706617 DOI: 10.1371/journal.pone.0117817
    Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5 × 10(4) plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans.
    Matched MeSH terms: Disease Models, Animal; Disease Progression
  8. Miah G, Rafii MY, Ismail MR, Puteh AB, Rahim HA, Latif MA
    C. R. Biol., 2015 Feb;338(2):83-94.
    PMID: 25553855 DOI: 10.1016/j.crvi.2014.11.003
    Backcross breeding is the most commonly used method for incorporating a blast resistance gene into a rice cultivar. Linkage between the resistance gene and undesirable units can persist for many generations of backcrossing. Marker-assisted backcrossing (MABC) along with marker-assisted selection (MAS) contributes immensely to overcome the main limitation of the conventional breeding and accelerates recurrent parent genome (RPG) recovery. The MABC approach was employed to incorporate (a) blast resistance gene(s) from the donor parent Pongsu Seribu 1, the blast-resistant local variety in Malaysia, into the genetic background of MR219, a popular high-yielding rice variety that is blast susceptible, to develop a blast-resistant MR219 improved variety. In this perspective, the recurrent parent genome recovery was analyzed in early generations of backcrossing using simple sequence repeat (SSR) markers. Out of 375 SSR markers, 70 markers were found polymorphic between the parents, and these markers were used to evaluate the plants in subsequent generations. Background analysis revealed that the extent of RPG recovery ranged from 75.40% to 91.3% and from 80.40% to 96.70% in BC1F1 and BC2F1 generations, respectively. In this study, the recurrent parent genome content in the selected BC2F2 lines ranged from 92.7% to 97.7%. The average proportion of the recurrent parent in the selected improved line was 95.98%. MAS allowed identification of the plants that are more similar to the recurrent parent for the loci evaluated in backcross generations. The application of MAS with the MABC breeding program accelerated the recovery of the RP genome, reducing the number of generations and the time for incorporating resistance against rice blast.
    Matched MeSH terms: Disease Resistance/genetics
  9. Hilmi I, Jaya F, Chua A, Heng WC, Singh H, Goh KL
    J Crohns Colitis, 2015 May;9(5):404-9.
    PMID: 25744112 DOI: 10.1093/ecco-jcc/jjv039
    Inflammatory bowel disease [IBD] is known to be rare in the Asia Pacific region but epidemiological studies are scarce.
    Matched MeSH terms: Crohn Disease/ethnology*
  10. Roohani K, Tan SW, Yeap SK, Ideris A, Bejo MH, Omar AR
    J Vet Sci, 2015;16(4):447-57.
    PMID: 25643805 DOI: 10.4142/jvs.2015.16.4.447
    A Newcastle disease virus (NDV) isolate designated IBS002 was isolated from a commercial broiler farm in Malaysia. The virus was characterised as a virulent strain based on the multiple basic amino acid motif of the fusion (F) cleavage site (112)RRRKGF(117) and length of the C-terminus extension of the hemagglutinin-neuraminidase (HN) gene. Furthermore, IBS002 was classified as a velogenic NDV with mean death time (MDT) of 51.2 h and intracerebral pathogenicity index (ICPI) of 1.76. A genetic distance analysis based on the full-length F and HN genes showed that both velogenic viruses used in this study, genotype VII NDV isolate IBS002 and genotype VIII NDV isolate AF2240-I, had high genetic variations with genotype II LaSota vaccine. In this study, the protection efficacy of the recombinant genotype VII NDV inactivated vaccine was also evaluated when added to an existing commercial vaccination program against challenge with velogenic NDV IBS002 and NDV AF2240-I in commercial broilers. The results indicated that both LaSota and recombinant genotype VII vaccines offered full protection against challenge with AF2240-I. However, the LaSota vaccine only conferred partial protection against IBS002. In addition, significantly reduced viral shedding was observed in the recombinant genotype VII-vaccinated chickens compared to LaSota-vaccinated chickens.
    Matched MeSH terms: Newcastle Disease; Newcastle disease virus
  11. Li H, Teo YY, Tan EK
    Mov Disord, 2015 Sep;30(10):1335-42.
    PMID: 25758099 DOI: 10.1002/mds.26176
    Reproducing genomewide association studies findings in different populations is challenging, because the reproducibility fundamentally relies on the similar patterns of linkage disequilibrium between the unknown causal variants and the genotyped single-nucleotide polymorphisms (SNPs).
    Matched MeSH terms: Parkinson Disease/genetics*
  12. Zulkhernain NS, Teo SH, Patel V, Tan PJ
    Curr Cancer Drug Targets, 2014;14(8):764-73.
    PMID: 25348017 DOI: 10.2174/1568009614666141028121347
    Targeted therapy, the treatment of cancer based on an underlying genetic alteration, is rapidly gaining favor as the preferred therapeutic approach. To date, although natural products represent a rich resource of bio-diverse drug candidates, only a few have been identified to be effective as targeted cancer therapies largely due to the incompatibilities to current high-throughput screening methods. In this article, we review the utility of a zebrafish developmental screen for bioactive natural product-based compounds that target signaling pathways that are intimately shared with those in humans. Any bioactive compound perturbing signaling pathways identified from phenotypic developmental defects in zebrafish embryos provide an opportunity for developing targeted therapies for human cancers. This model provides a promising tool in the search for targeted cancer therapeutics from natural products.
    Matched MeSH terms: Disease Models, Animal*
  13. Syed-Hussain SS, Howe L, Pomroy WE, West DM, Hardcastle M, Williamson NB
    Vet Parasitol, 2015 Mar 15;208(3-4):150-8.
    PMID: 25638717 DOI: 10.1016/j.vetpar.2014.12.036
    Recent reports indicate N. caninum has a possible role in causing abortions in sheep in New Zealand. Knowledge about the mode of transmission of neosporosis in sheep in New Zealand is limited. This study aimed to determine the rate of vertical transmission that would occur in lambs born from experimentally inoculated ewes and to determine if previous inoculation would protect the lambs from N. caninum infection. A group of 50 ewes was divided into 2 groups with one group being inoculated with 5×10(6) N. caninum tachyzoites prior to pregnancy in Year 1. In Year 2, each of these groups was subdivided into 2 groups with one from each original group being inoculated with 1×10(7) N. caninum tachyzoites on Day 120 of gestation. Inoculation of N. caninum tachyzoites into ewes prior to mating resulted in no congenital transmission in lambs born in Year 1 but without further inoculation, 7 out of 11 lambs in Year 2 were positive for N. caninum infection. Ewes that were inoculated in both years resulted in all 12 lambs born in Year 2 being positive for N. caninum infection. This indicates that previous inoculation in Year 1 did not result in any vertical transmission in that year but did not provide any protection against vertical transmission in Year 2. These results suggest that vertical transmission occurs readily once the ewe is infected.
    Matched MeSH terms: Infectious Disease Transmission, Vertical/veterinary*
  14. Grigg MJ, William T, Drakeley CJ, Jelip J, von Seidlein L, Barber BE, et al.
    BMJ Open, 2014 Aug 22;4(8):e006004.
    PMID: 25149186 DOI: 10.1136/bmjopen-2014-006004
    INTRODUCTION: Plasmodium knowlesi has long been present in Malaysia, and is now an emerging cause of zoonotic human malaria. Cases have been confirmed throughout South-East Asia where the ranges of its natural macaque hosts and Anopheles leucosphyrus group vectors overlap. The majority of cases are from Eastern Malaysia, with increasing total public health notifications despite a concurrent reduction in Plasmodium falciparum and P. vivax malaria. The public health implications are concerning given P. knowlesi has the highest risk of severe and fatal disease of all Plasmodium spp in Malaysia. Current patterns of risk and disease vary based on vector type and competence, with individual exposure risks related to forest and forest-edge activities still poorly defined. Clustering of cases has not yet been systematically evaluated despite reports of peri-domestic transmission and known vector competence for human-to-human transmission.

    METHODS AND ANALYSIS: A population-based case-control study will be conducted over a 2-year period at two adjacent districts in north-west Sabah, Malaysia. Confirmed malaria cases presenting to the district hospital sites meeting relevant inclusion criteria will be requested to enrol. Three community controls matched to the same village as the case will be selected randomly. Study procedures will include blood sampling and administration of household and individual questionnaires to evaluate potential exposure risks associated with acquisition of P. knowlesi malaria. Secondary outcomes will include differences in exposure variables between P. knowlesi and other Plasmodium spp, risk of severe P. knowlesi malaria, and evaluation of P. knowlesi case clustering. Primary analysis will be per protocol, with adjusted ORs for exposure risks between cases and controls calculated using conditional multiple logistic regression models.

    ETHICS: This study has been approved by the human research ethics committees of Malaysia, the Menzies School of Health Research, Australia, and the London School of Hygiene and Tropical Medicine, UK.

    Matched MeSH terms: Disease Vectors*
  15. Panagiotou OA, Travis RC, Campa D, Berndt SI, Lindstrom S, Kraft P, et al.
    Eur Urol, 2015 Apr;67(4):649-57.
    PMID: 25277271 DOI: 10.1016/j.eururo.2014.09.020
    BACKGROUND: No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS).

    OBJECTIVE: To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer.

    DESIGN, SETTING, AND PARTICIPANTS: SNPs implicated in any phenotype other than prostate cancer (p≤10(-7)) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24,534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated.

    RESULTS AND LIMITATIONS: A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p=1.6×10(-6)), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95% CI 1.16-1.27; p=3.22×10(-18)). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86-0.94; p=2.5×10(-6)). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12, 95% CI 1.06-1.19; p=4.67×10(-5)); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL.

    CONCLUSIONS: We did not identify new SNPs for aggressive prostate cancer. However, rs16844874 may provide preliminary genetic evidence on the role of the glycine pathway in prostate cancer etiology.

    PATIENT SUMMARY: We evaluated whether genetic variants associated with several traits are linked to the risk of aggressive prostate cancer. No new such variants were identified.

    Matched MeSH terms: Disease Progression; Genetic Predisposition to Disease
  16. Abdullah JM, Mustafa Z, Ideris A
    Biomed Res Int, 2014;2014:386470.
    PMID: 25243137 DOI: 10.1155/2014/386470
    Glioblastoma multiforme (GBM), or grade IV glioma, is one of the most lethal forms of human brain cancer. Current bioscience has begun to depict more clearly the signalling pathways that are responsible for high-grade glioma initiation, migration, and invasion, opening the door for molecular-based targeted therapy. As such, the application of viruses such as Newcastle disease virus (NDV) as a novel biological bullet to specifically target aberrant signalling in GBM has brought new hope. The abnormal proliferation and aggressive invasion behaviour of GBM is reported to be associated with aberrant Rac1 protein signalling. NDV interacts with Rac1 upon viral entry, syncytium induction, and actin reorganization of the infected cell as part of the replication process. Ultimately, intracellular stress leads the infected glioma cell to undergo cell death. In this review, we describe the characteristics of malignant glioma and the aberrant genetics that drive its aggressive phenotype, and we focus on the use of oncolytic NDV in GBM-targeted therapy and the interaction of NDV in GBM signalling that leads to inhibition of GBM proliferation and invasion, and subsequently, cell death.
    Matched MeSH terms: Newcastle disease virus/physiology*
  17. Mustapha F, Omar Z, Mihat O, Md Noh K, Hassan N, Abu Bakar R, et al.
    BMC Public Health, 2014;14 Suppl 2:S4.
    PMID: 25080846 DOI: 10.1186/1471-2458-14-S2-S4
    The prevalence of non-communicable diseases (NCDs) and NCD risk factors in Malaysia have risen substantially in the last two decades. The Malaysian Ministry of Health responded by implementing, "The National Strategic Plan for Non-Communicable Diseases (NSP-NCD) 2010-2014", and the "NCD Prevention 1Malaysia" (NCDP-1M) programme. This paper outlines the primary health system context in which the NCDP-1M is framed. We also discuss the role of community in facilitating the integration of this programme, and outline some of the key challenges in addressing the sustainability of the plan over the next few years. The paper thus provides an analysis of an integration of a programme that involved a multi-sectoral approach with the view to contributing to a broader discourse on the development of responsive health systems.
    Matched MeSH terms: Chronic Disease/prevention & control*
  18. Italiano CM, Wong KT, AbuBakar S, Lau YL, Ramli N, Syed Omar SF, et al.
    PLoS Negl Trop Dis, 2014 May;8(5):e2876.
    PMID: 24854350 DOI: 10.1371/journal.pntd.0002876
    From the 17th to 19th January 2012, a group of 92 college students and teachers attended a retreat in a hotel located on Pangkor Island, off the west coast of Peninsular Malaysia. Following the onset of symptoms in many participants who presented to our institute, an investigation was undertaken which ultimately identified Sarcocystis nesbitti as the cause of this outbreak.
    Matched MeSH terms: Disease Outbreaks*
  19. Dups J, Middleton D, Long F, Arkinstall R, Marsh GA, Wang LF
    Virol J, 2014;11:102.
    PMID: 24890603 DOI: 10.1186/1743-422X-11-102
    Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disease recrudescence. In this study we investigated the possibility of developing a similar model of Nipah virus encephalitis.
    Matched MeSH terms: Disease Models, Animal*
  20. 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.
    Matched MeSH terms: Non-alcoholic Fatty Liver Disease/genetics*
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