Displaying publications 1 - 20 of 188 in total

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  1. Huntington disease-like phenotype in a patient with ANO3 mutation
    Koya Kutty S, Mulroy E, Magrinelli F, Di Lazzaro G, Latorre A, Bhatia KP
    Parkinsonism Relat Disord, 2021 09;90:120-122.
    PMID: 33640251 DOI: 10.1016/j.parkreldis.2021.02.022
    Matched MeSH terms: Huntington Disease/genetics*
  2. Fulltext Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders
    Andlauer TFM, Guzman-Parra J, Streit F, Strohmaier J, González MJ, Gil Flores S, et al.
    Mol Psychiatry, 2021 Apr;26(4):1286-1298.
    PMID: 31712721 DOI: 10.1038/s41380-019-0558-2
    Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  3. Uncovering the genetic basis of Parkinson's disease globally: from discoveries to the clinic
    Lim SY, Tan AH, Ahmad-Annuar A, Okubadejo NU, Lohmann K, Morris HR, et al.
    Lancet Neurol, 2024 Dec;23(12):1267-1280.
    PMID: 39447588 DOI: 10.1016/S1474-4422(24)00378-8
    Knowledge on the genetic basis of Parkinson's disease has grown tremendously since the discovery of the first monogenic form, caused by a mutation in α-synuclein, and with the subsequent identification of multiple other causative genes and associated loci. Genetic studies provide insights into the phenotypic heterogeneity and global distribution of Parkinson's disease. By shedding light on the underlying biological mechanisms, genetics facilitates the identification of new biomarkers and therapeutic targets. Several clinical trials of genetics-informed therapies are ongoing or imminent. International programmes in populations who have been under-represented in Parkinson's disease genetics research are fostering collaboration and capacity-building, and have already generated novel findings. Many challenges remain for genetics research in these populations, but addressing them provides opportunities to obtain a more complete and equitable understanding of Parkinson's disease globally. These advances facilitate the integration of genetics into the clinic, to improve patient management and personalised medicine.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  4. EPOXID HYDROLASE SINGLE GENE POLYMORPHISM (RS1051740) AND SEVERITY OF CHRONIC OBSTRUCTIVE DISEASE
    Antonova I, Gridnyev O, Galchinskaya V
    Wiad Lek, 2022;75(11 pt 2):2779-2784.
    PMID: 36591768 DOI: 10.36740/WLek202211211
    OBJECTIVE: The aim: The aim of the present study was to establish a link between polymorphic variants of the microsomal epoxide hydrolase gene and the severity of COPD in patients with COPD and coronary heart disease.

    PATIENTS AND METHODS: Materials and methods: The study included 128 patients with COPD and IHD, who were divided into two groups: group 1 included 72 patients with in¬frequent exacerbations of COPD (0-1 per year) and group 2 included 56 patients with frequent exacerbations of COPD (exacerbation of COPD ≥2 per year). The control groups consisted of 15 smokers without COPD and IHD, 11 practically healthy non-smokers and 11 patients with IHD who do not smoke. All patients underwent DNA isolation and purification, followed by determination of the Tyr113His polymorphism of the EPHX1 microsomal epoxide hydrolase gene (rs1051740).

    RESULTS: Results: There was a significant association of the carriage of the CC genotype of the EPHX1 gene in patients with COPD and IHD (RO = 21.326 [95.0% CI 4.217-107.846], p <0.001) with a more severe course of COPD compared with the TT genotype of the EPHX1 gene.

    CONCLUSION: Conclusions: Patients with COPD and coronary heart disease who were carriers of a homozygous variant СС of the EPHX1 gene have a reliable association with a more severe course of COPD with frequent exacerbations (higher class according to GOLD classification and more severe symptoms of COPD according to the СAT questionnaire).

    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  5. Common variant in the glucokinase regulatory gene rs780094 and risk of nonalcoholic fatty liver disease: a meta-analysis
    Zain SM, Mohamed Z, Mohamed R
    J Gastroenterol Hepatol, 2015 Jan;30(1):21-7.
    PMID: 25167786 DOI: 10.1111/jgh.12714
    BACKGROUND AND AIM: Although studies have suggested that rs780094, a common variant in the glucokinase regulatory (GCKR) gene to be associated with type 2 diabetes, obesity, and their related traits, the genetic basis of the association between GCKR rs780094 and nonalcoholic fatty liver disease (NAFLD) is still being examined. This meta-analysis was performed to evaluate the effect strength caused by GCKR rs780094 on NAFLD.
    METHODS: We searched Medline, PubMed, Scopus, and Embase for relevant articles published up to April 2014. Data were extracted, and summary estimates of the association between GCKR rs780094 and NAFLD were examined. Heterogeneity and publication bias were also examined.
    RESULTS: This meta-analysis incorporated a total of 2091 NAFLD cases and 3003 controls from five studies. Overall, the pooled result indicated that the GCKR rs780094 was significantly associated with increased risk of NAFLD (additive: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.14-1.36, P 
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*; Non-alcoholic Fatty Liver Disease/genetics*
  6. Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a 'thrifty' allele?
    Corbo RM, Scacchi R
    Ann. Hum. Genet., 1999 Jul;63(Pt 4):301-10.
    PMID: 10738542
    Apolipoprotein E (APOE = gene, apoE = protein) plays a central role in plasma lipoprotein metabolism and in lipid transport within tissues. The APOE shows a genetic polymorphism determined by three common alleles, APOE*2, APOE*3, APOE*4 and the product of the three alleles differs in several functional properties. APOE is involved in the development of certain pathological conditions. In particular, the APOE*4 allele is a risk factor for susceptibility to coronary artery disease (CAD) and Alzheimer's Disease (AD). In the present study we analyzed the APOE allele distribution in the world. The APOE*3 is the most frequent in all the human groups, especially in populations with a long-established agricultural economy like those of the Mediterranean basin (0.849-0.898). The frequency of APOE*4, the ancestral allele, remains higher in populations like Pygmies (0.407) and Khoi San (0.370), aborigines of Malaysia (0.240) and Australia (0.260), Papuans (0.368), some Native Americans (0.280), and Lapps (0.310) where an economy of foraging still exists, or food supply is (or was until the recent past) scarce and sporadically available. The APOE*2 frequency fluctuates with no apparent trend (0.145-0.02) and is absent in Native Americans. We suggest that the APOE*4, based on some functional properties it has and on its distribution among human populations, could be identified as a 'thrifty' allele. The exposure of APOE*4 to the contemporary environmental conditions (Western diet, longer lifespans) could have rendered it a susceptibility allele for CAD and AD. The absence of the association of APOE*4 with CAD and AD in Sub-Saharan Africans, and its presence in African Americans, seems to confirm this hypothesis.
    Matched MeSH terms: Alzheimer Disease/genetics; Coronary Disease/genetics
  7. Evaluation of novel Parkinson's disease candidate genes in the Chinese population
    Chew EGY, Liany H, Tan LCS, Au WL, Prakash KM, Annuar AA, et al.
    Neurobiol Aging, 2019 02;74:235.e1-235.e4.
    PMID: 30337193 DOI: 10.1016/j.neurobiolaging.2018.09.013
    Recent whole-exome sequencing studies in European patients with Parkinson's disease (PD) have identified potential risk variants across 33 novel PD candidate genes. We aim to determine if these reported candidate genes are similarly implicated in Asians by assessing common, rare, and novel nonsynonymous coding variants by sequencing all 33 genes in 198 Chinese samples and genotyping coding variants in an independent set of 9756 Chinese samples. We carried out further targeted sequencing of CD36 in an additional 576 Chinese and Korean samples. We found that only 8 of 43 reported risk variants were polymorphic in our Chinese samples. We identified several heterozygotes for rare loss-of-function mutations, including the reported CD36 p.Gln74Ter variant, in both cases and controls. We also observed 2 potential compound heterozygotes among PD cases for rare loss-of-function mutations in CD36 and SSPO. The other reported variants were common in East Asians and not associated with PD, completely absent, or only found in controls. Therefore, the 33 reported candidate genes and associated variants are unlikely to confer significant PD risk in the East Asian population.
    Matched MeSH terms: Parkinson Disease/genetics*; Genetic Predisposition to Disease/genetics*
  8. Association between inflammatory bowel disease gene 5 (IBD5) and interleukin-23 receptor (IL23R) genetic polymorphisms in Malaysian patients with Crohn's disease
    Chua KH, Hilmi I, Lian LH, Patmanathan SN, Hoe SZ, Lee WS, et al.
    J Dig Dis, 2012 Sep;13(9):459-65.
    PMID: 22908971 DOI: 10.1111/j.1751-2980.2012.00617.x
    This study was aimed to investigate the possible association of Crohn's disease (CD) with inflammatory bowel disease gene 5 (IBD5) IGR2198a_1 (rs11739135), IGR2096a_1 (rs12521868) and interleukin-23 receptor (IL23R) genetic variant (rs1004819) in the Malaysian population.
    Matched MeSH terms: Crohn Disease/genetics*
  9. Letter regarding "CD95 rs1800682 polymorphism and cervical cancer risk: evidence from a meta-analysis" by Zhang et al
    Tan SC
    Tumour Biol., 2015 Nov;36(11):8275-6.
    PMID: 26515334 DOI: 10.1007/s13277-015-4330-1
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  10. Fulltext Psychiatric presentation of Huntington's disease in a Malaysian family
    Chin CN, S'ng KH, Philip G, Rosdinom R, Wahidah A
    Med J Malaysia, 1996 Mar;51(1):153-6.
    PMID: 10968000
    A 32-year-old Chinese lady presented to the Psychiatric Clinic with a history of change in personality for 2 years and abnormal movements for a year. After thorough investigations and observation a diagnosis of Huntington's Disease was made. Her elder brother was traced and found to have Huntington's Disease as well. He had a long standing history of antisocial behaviour and substance abuse long before the onset of the choreiform movements. Her younger brother also has choreiform movements for the last 2 years and had recent change in personality. Their mother also had abnormal movements and was recorded to be depressed and attempted suicide. The maternal grandfather had a mental illness and was warded at a mental institution till his death in 1942. Psychiatric presentation of Huntington's Disease in this Malaysian family is prominent and preceded the characteristic movements in the present generation.
    Matched MeSH terms: Huntington Disease/genetics*
  11. Fulltext The spectrum of association in HLA region with rheumatoid arthritis in a diverse Asian population: evidence from the MyEIRA case-control study
    Tan LK, Too CL, Diaz-Gallo LM, Wahinuddin S, Lau IS, Heselynn H, et al.
    Arthritis Res Ther, 2021 01 30;23(1):46.
    PMID: 33514426 DOI: 10.1186/s13075-021-02431-z
    BACKGROUND: Fine-mapping of human leukocyte antigen (HLA) region for rheumatoid arthritis (RA) risk factors has identified several HLA alleles and its corresponding amino acid residues as independent signals (i.e., HLA-A, HLA-B, HLA-DPB1, and HLA-DQA1 genes), in addition to the well-established genetic factor in HLA-DRB1 gene. However, this was mainly performed in the Caucasian and East Asian populations, and data from different Asian regions is less represented. We aimed to evaluate whether there are independent RA risk variants in both anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients from the multi-ethnic Malaysian population, using the fine-mapping of HLA region strategy.

    METHODS: We imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region.

    RESULTS: We confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30-5.49, PGWAS = 7.22 × 10-29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37-0.62, PGWAS = 2.58 × 10-08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09-0.30, PGWAS = 1.60 × 10-09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia.

    CONCLUSIONS: Our results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.

    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  12. Celiac disease screening in southern and East Asia
    Makharia GK
    Dig Dis, 2015;33(2):167-174.
    PMID: 25925919 DOI: 10.1159/000369537
    Until 1970s, celiac disease (CD) was considered to be an uncommon disease except in Western Europe. The global epidemiology of CD continues to evolve with improvement in the diagnostic tests, simplification of the diagnostic criteria and increase in awareness about the disease. The Asian region is currently at the crossroads of the frontier of knowledge and awareness of CD. In many Asian nations, CD is still considered to be either nonexistent or very rare. A notable exception is India, where CD has been well recognized, especially in the northern part, and 2 population-based studies have revealed a prevalence of 0.3-1.04%. Initial reports from Malaysia, China, Japan and Singapore suggest the existence of CD in these countries. Furthermore, a meta-analysis of the predisposing factors predicts a high probability of occurrence of CD in fair numbers in China. There are no formal reports on CD from Malaysia, Indonesia, Korea, Taiwan and many other nations in this region. With the impending CD epidemic in Asia, there are many challenges. Some of the efforts which are required include determination of prevalence of CD across the region, spreading of awareness among physicians and patients, training of dieticians for proper counseling and supervision of patients, creation of gluten-free food infrastructure in the food supply and creation of patient advocacy organizations. Although the absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years/decades. It is thus appropriate that the medical community across Asia define the extent of the problem and get prepared to handle the impending CD epidemic.
    Matched MeSH terms: Celiac Disease/genetics
  13. A case of early-onset familial Alzheimer's disease with both APP and novel PSEN2 mutations presenting with non-amnestic features
    Chee KY, Yee OK, Gaillard F, Velakoulis D, Mohd Zain NR, Yogendren L, et al.
    Aust N Z J Psychiatry, 2017 Dec;51(12):1252-1253.
    PMID: 28762277 DOI: 10.1177/0004867417722642
    Matched MeSH terms: Alzheimer Disease/genetics*
  14. Fulltext Mutation Study of Malaysian Patients with Ornithine Transcarbamylase Deficiency: Clinical, Molecular, and Bioinformatics Analyses of Two Novel Missense Mutations of the OTC Gene
    Ali EZ, Zakaria Y, Mohd Radzi MA, Ngu LH, Jusoh SA
    Biomed Res Int, 2018;2018:4320831.
    PMID: 30175132 DOI: 10.1155/2018/4320831
    Ornithine transcarbamylase deficiency (OTCD), an X-linked disorder that results from mutations in the OTC gene, causes hyperammonemia and leads to various clinical manifestations. Mutations occurring close to the catalytic site of OTCase can cause severe OTCD phenotypes compared with those caused by mutations occurring on the surface of this protein. In this study, we report two novel OTC missense mutations, Q171H and N199H, found in Malaysian patients. Q171H and N199H caused neonatal onset OTCD in a male and late OTCD in a female, respectively. In silico predictions and molecular docking were performed to examine the effect of these novel mutations, and the results were compared with other 30 known OTC mutations. In silico servers predicted that Q171H and N199H, as well as 30 known missense mutations, led to the development of OTCD. Docking analysis indicated that N-(phosphonoacetyl)-L-ornithine (PALO) was bound to the catalytic site of OTCase mutant structure with minimal conformational changes. However, the mutations disrupted interatomic interactions in the catalytic site. Therefore, depending on the severity of disruption occurring at the catalytic site, the mutation may affect the efficiency of mechanism and functions of OTCase.
    Matched MeSH terms: Ornithine Carbamoyltransferase Deficiency Disease/genetics*
  15. miR-124 and Parkinson's disease: A biomarker with therapeutic potential
    Angelopoulou E, Paudel YN, Piperi C
    Pharmacol Res, 2019 12;150:104515.
    PMID: 31707035 DOI: 10.1016/j.phrs.2019.104515
    Parkinson's disease (PD) is a multifactorial disorder, attributed to a complex interplay between genetic and epigenetic factors. Although the exact etiology of the disease remains elusive, dysregulation of signaling pathways implicated in cell survival, apoptosis, protein aggregation, mitochondrial dysfunction, autophagy, oxidative damage and neuroinflammation, contributes to its pathogenesis. MicroRNAs (miRs) are endogenous short non-coding RNA molecules that negatively regulate gene expression at a post-transcriptional level. MiR-124 is one of the most abundantly expressed miRs in the brain that participates in neurogenesis, synapse morphology, neurotransmission, inflammation, autophagy and mitochondrial function. Accumulating pre-clinical evidence shows that miR-124 may act through calpain 1/p25/cyclin-dependent kinases 5 (CDK5), nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), Bcl-2-interacting mediator of cell death (Bim), 5' adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK)-mediated pathways to regulate cell survival, apoptosis, autophagy, mitochondrial dysfunction, oxidative damage and neuroinflammation in PD. Moreover, clinical evidence indicates that reduced plasma miR-124 levels may serve as a potential diagnostic biomarker in PD. This review provides an update of the pathogenic implication of miR-124 activity in PD and discusses its targeting potential for the development of future therapeutic strategies.
    Matched MeSH terms: Parkinson Disease/genetics*
  16. Lafora disease in a Malaysian with a rare mutation in the EPM2A gene
    Tee SK, Ong TL, Aris A, See SML, Leong HY, Khalid MKNM, et al.
    Seizure, 2019 Apr;67:78-81.
    PMID: 30947044 DOI: 10.1016/j.seizure.2019.03.012
    Matched MeSH terms: Lafora Disease/genetics*
  17. Emerging Roles of Sirtuin 6 in Alzheimer's Disease
    Mohamad Nasir NF, Zainuddin A, Shamsuddin S
    J Mol Neurosci, 2018 Feb;64(2):157-161.
    PMID: 29260452 DOI: 10.1007/s12031-017-1005-y
    Alzheimer's disease (AD) is a neurodegenerative disease that is imposing an increasing burden on society. Currently, AD is the leading cause of senile dementia worldwide. Despite the long existence of AD, there is lack of therapies for AD, suggesting that new and effective treatment strategy must be explored. At present, sirtuin pathway has attracted attention from the researchers due to its promising results in laboratory models of aging. In addition, our understanding in the roles of sirtuin 6 in AD has expanded. It has been identified to be involved in telomere maintenance, DNA repair, genome integrity, energy metabolism, and inflammation, which ultimately regulate life span. Recent findings also demonstrate that sirtuin 6 is lacking in AD patients, proposing that it can be a new potential therapeutic target in AD. Therefore, exploring on how sirtuin 6 is related in AD manifestation may accelerate the research of AD further and benefits future AD patients. Keeping that in mind, this review aims to highlight the possible roles of sirtuin 6 in AD manifestation.
    Matched MeSH terms: Alzheimer Disease/genetics
  18. Association between genetic polymorphisms in interferon regulatory factor 5 (IRF5) gene and Malaysian patients with Crohn's disease
    Chua KH, Lian LH, Khor WC, Lee WS, Hilmi I, Goh KL, et al.
    J Dig Dis, 2015 Apr;16(4):205-16.
    PMID: 25564941 DOI: 10.1111/1751-2980.12229
    The study aimed to investigate the association between the interferon regulatory factor 5 (IRF5) gene polymorphisms and the onset of Crohn's disease (CD) in a Malaysian cohort.
    Matched MeSH terms: Crohn Disease/genetics*; Genetic Predisposition to Disease/genetics*
  19. HLA-DRA rs3129882 A/G polymorphism was not a risk factor for Parkinson's disease in Chinese-based populations: a meta-analysis
    Ma ZG, Liu TW, Bo YL
    Int J Neurosci, 2015 Apr;125(4):241-6.
    PMID: 24849299 DOI: 10.3109/00207454.2014.926349
    Many studies have evaluated the association between the HLA-DRA rs3129882 A/G polymorphism and risk for Parkinson's disease (PD) in Chinese-based populations, however, published data remain inconclusive. Therefore, we performed a meta-analysis from all relevant studies to evaluate an association of HLA-DRA rs3129882 A/G polymorphism with susceptibility to PD.
    Matched MeSH terms: Parkinson Disease/genetics*; Genetic Predisposition to Disease/genetics*
  20. Fulltext Current Concepts of Neurodegenerative Mechanisms in Alzheimer's Disease
    Magalingam KB, Radhakrishnan A, Ping NS, Haleagrahara N
    Biomed Res Int, 2018;2018:3740461.
    PMID: 29707568 DOI: 10.1155/2018/3740461
    Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer's disease is characterized by the abnormal accumulation of extracellular amyloid-β plaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.
    Matched MeSH terms: Alzheimer Disease/genetics; Parkinson Disease/genetics
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