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  1. Wan CL, Zainal NZ, Lian LH, Mohamed Z
    Psychiatry Res, 2011 Aug 30;189(1):67-71.
    PMID: 21414668 DOI: 10.1016/j.psychres.2011.02.008
    The catechol-O-methyltransferase (COMT) gene is a candidate gene for schizophrenia as its encoded enzyme is involved in the metabolic inactivation of dopamine and noradrenaline. Several molecular genetic studies thus far have demonstrated that the COMT functional polymorphism of Val158Met is susceptible with schizophrenia. Hence, the present study aims to determine this genetic association of this SNP in the three major ethnic groups of the Malaysian population. A total of 317 patients (79 Malays, 154 Chinese and 84 Indians) meeting DSM-IV criteria for schizophrenia and 417 healthy subjects (160 Malays, 164 Chinese and 93 Indians) were recruited. A PCR-RFLP method was used to determine the genotypes and alleles present. We found a significant association of genotypes within the total pooled samples, as well as in the female subgroup, with a higher frequency of heterozygotes in schizophrenia subjects. However, there were no significant differences in allele and genotype frequency between the schizophrenic patients and normal controls in all three ethnic groups. Our current findings suggest that the Val158Met polymorphism has a weak association with schizophrenia in the Malaysian population and does not play a major role in conferring susceptibility to the schizophrenia in any of the three major local ethnicities.
    Matched MeSH terms: Genetic Predisposition to Disease*
  2. Salahshourifar I, Halim AS, Wan Sulaiman WA, Zilfalil BA
    J Hum Genet, 2011 Nov;56(11):755-8.
    PMID: 21866112 DOI: 10.1038/jhg.2011.95
    Oral clefts are clinically and genetically heterogeneous disorders that are influenced by both genetic and environmental factors. The present family-based association study investigated the role of the MSX1 and TGFB3 genes in the etiology of non-syndromic oral cleft in a Malay population. No transmission distortion was found in the transmission disequilibrium analysis for either MSX1-CA or TGFB3-CA intragenic markers, whereas TGFB3-CA exhibited a trend to excess maternal transmission. In sequencing the MSX1 coding regions in 124 patients with oral cleft, five variants were found, including three known variants (A34G, G110G and P147Q) and two novel variants (M37L and G267A). The P147Q and M37L variants were not observed in 200 control chromosomes, whereas G267A was found in one control sample, indicating a very rare polymorphic variant. Furthermore, the G110G variant displayed a significant association between patients with non-syndromic cleft lip, with or without cleft palate, and normal controls (P=0.001, odds ratio=2.241, 95% confidence interval, 1.357-3.700). Therefore, these genetic variants may contribute, along with other genetic and environmental factors, to this condition.
    Matched MeSH terms: Genetic Predisposition to Disease*
  3. Molouki A, Hsu YT, Jahanshiri F, Abdullah S, Rosli R, Yusoff K
    Virol J, 2011;8:385.
    PMID: 21810274 DOI: 10.1186/1743-422X-8-385
    The underlying mechanisms by which Newcastle disease virus (NDV) kills cancer cells are still unclear. Recent discoveries have shown that many viruses contain Bcl-2 homology-like domains which enabled their interaction with Bcl-2 family members, and thereby accounting for their virulence and pathogenicity. Alignment of the protein sequences of Malaysian strain of NDV, known as AF2240, with those from members of the human Bcl-2 family showed many similar regions; most notably we found that its matrix (AF2240-M) protein, large (AF2240-L) protein and fusion (AF2240-F) protein all contain BH3-like regions. In addition, there are BH1-like domains in these proteins, where AF2240-F and Mcl-1 share 55% identity within this region. To further investigate our hypothesis that the presence of the BH3-like domains in these proteins may convey cytotoxicity, AF2240-M and AF2240-F genes were cloned into pFLAG and pEGFP.N2 vectors and transfected into HeLa cells. The expression of these constructs promoted cell death. As shown by flow cytometry, AF2240-M protein with deleted BH3-like region showed five-fold decrease in apoptosis. Moreover, the construct containing the N-terminal of AF2240-M showed nearly the same cell death rate as to that of the full-length protein, strongly suggesting that the BH3-like domain within this protein participates in promoting cell death. Moreover, AF2240-M transfection promoted Bax redistribution to mitochondria. Therefore, to determine whether there is any direct interaction between NDV viral proteins with some members of the Bcl-2 family, various constructs were co-transfected into HeLa cells. Co-immunoprecipitation trials showed that the AF2240-M indeed directly interacted with Bax protein via its BH3-domain, as the mutant proteins failed to interact with Bax. AF2240-F failed to interact with any of the tested proteins, although Bcl-XL slowed down the rate of cell death caused by this construct by nearly five-fold. In a parallel experiment, the level of expression of endogenous Bax and Bcl-2 after infection of HeLa cells with NDV was assessed by qRT-PCR, but no statistically significant change was observed. Consequently, the Bax/Bcl-2 ratio at the mRNA level did not alter. Overall, our study has shed additional light into the mechanisms by which NDV induces apoptosis.
    Matched MeSH terms: Newcastle disease virus/pathogenicity*
  4. Chua KH, Puah SM, Chew CH, Wong CH, Goh KL
    Pancreatology, 2011;11(4):441-4.
    PMID: 21952138 DOI: 10.1159/000330943
    Hereditary pancreatitis (HP) is a very rare form of early-onset chronic pancreatitis, which usually begins in childhood with a variable spectrum of severity of disease. HP is commonly caused by variants/mutations in the PRSS1 gene as reported in many studies. Therefore, in this study, we aimed to investigate the possible association of PRSS1 gene variants/mutations in a Malaysian Chinese family with HP.
    Matched MeSH terms: Genetic Predisposition to Disease*
  5. Tee SF, Tang PY, Loh HC
    Psychiatry Res, 2012 Jan 30;195(1-2):83-4.
    PMID: 21872942 DOI: 10.1016/j.psychres.2011.07.039
    The present study included a total 261 patients with schizophrenia and 261 healthy controls to replicate the genetic association between the cathechol-o-methyltransferase gene and schizophrenia using a haplotype block-based gene-tagging. The G-G-G haplotype was found to show a highly significant association with schizophrenia.
    Matched MeSH terms: Genetic Predisposition to Disease*
  6. Sambanthamurthi R, Tan Y, Sundram K, Hayes KC, Abeywardena M, Leow SS, et al.
    Br J Nutr, 2011 Dec;106(11):1664-75.
    PMID: 21736778 DOI: 10.1017/S0007114511002133
    It is well established that plant phenolics elicit various biological activities, with positive effects on health. Palm oil production results in large volumes of aqueous by-products containing phenolics. In the present study, we describe the effects of oil palm phenolics (OPP) on several degenerative conditions using various animal models. OPP reduced blood pressure in a NO-deficient rat model, protected against ischaemia-induced cardiac arrhythmia in rats and reduced plaque formation in rabbits fed an atherogenic diet. In Nile rats, a spontaneous model of the metabolic syndrome and type 2 diabetes, OPP protected against multiple aspects of the syndrome and diabetes progression. In tumour-inoculated mice, OPP protected against cancer progression. Microarray studies on the tumours showed differential transcriptome profiles that suggest anti-tumour molecular mechanisms involved in OPP action. Thus, initial studies suggest that OPP may have potential against several chronic disease outcomes in mammals.
    Matched MeSH terms: Disease Models, Animal*
  7. Schmidt HM, Ha DM, Taylor EF, Kovach Z, Goh KL, Fock KM, et al.
    J Gastroenterol Hepatol, 2011 Dec;26(12):1725-32.
    PMID: 21649724 DOI: 10.1111/j.1440-1746.2011.06799.x
    BACKGROUND AND AIM: The contribution of human genetic polymorphisms to Helicobacter pylori infection and gastric cancer (GC) development remains unclear due to geographic variation in the association between specific host genetic polymorphisms and GC. In the current study we investigated the association between polymorphisms related to immune and cancer-related pathways and H. pylori infection among the major ethnicities, Chinese, Malay and Indian, resident in Singapore and Malaysia as well as the association between these polymorphisms and GC development in ethnic Chinese patients.

    METHODS: Thirty-four polymorphisms in 26 genes were typed by mass spectrometry in 422 patients undergoing endoscopy (162 Chinese, 113 Indian and 87 Malay controls and 60 Chinese GC cases). Patients were assessed for evidence of H. pylori infection. Odds ratios (OR) and confidence intervals (CI) were obtained using logistic regression models.

    RESULT: The prevalence of 16 polymorphisms varied significantly among the ethnicities. In the Chinese subgroup, nominally significant associations were shown between (i) EBBR2+1963G (rs1801200) and H. pylori infection (per-allele OR: 0.48, 95% CI 0.23, 0.98, P = 0.04), (ii) PTGS2-1195G (rs689466) and an increased risk of GC on adjusting for H. pylori status (OR: 1.53, 95% CI 0.99, 2.37, P = 0.05), and (iii) IL1B-1473C (rs1143623) and a decreased risk of GC (OR: 0.64, 95% CI 0.41, 0.99, P = 0.05). Borderline significant associations were seen between IL2-330G (rs2069762) (OR 1.45, 95% CI 0.95, 2.15, P = 0.06) and IL13-1111T (rs1800925) (OR 0.65, 95% CI 0.42, 1.01, P = 0.06) and H. pylori infection.

    CONCLUSION: These findings contribute to the understanding of the genetic variation between ethnicities, which may influence H. pylori susceptibility and the outcome of infection.

    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  8. Wong FL, Boo NY, Ainoon O, Wang MK
    Malays J Pathol, 2009 Dec;31(2):99-104.
    PMID: 20514852 MyJurnal
    This study aimed to determine the prevalence of four variants of organic anion transporter polypeptide 2 (OATP2) gene, and their association with severe hyperbilirubinemia.
    Matched MeSH terms: Genetic Predisposition to Disease*
  9. Chua KB
    Malays J Pathol, 2010 Dec;32(2):75-80.
    PMID: 21329177 MyJurnal
    An outbreak of acute febrile encephalitis affecting pig-farm workers and owners was recognized in peninsular Malaysia as early as September 1998. The outbreak was initially thought to be due to Japanese encephalitis (JE) virus and thus very intensive prevention, control and communication strategies directed at JE virus were undertaken by the Ministry of Health and Ministry of Agriculture of Malaysia. There was an immediate change in the prevention, control and communication strategies with focus and strategies on infected pigs as the source of infections for humans and other animals following the discovery of Nipah virus. Information and understanding the risks of Nipah virus infections and modes of transmission strengthened the directions of prevention, control and communication strategies. A number of epidemiological surveillances and field investigations which were broadly divided into 3 groups covering human health sector, animal health sector and reservoir hosts were carried out as forms of risk assessment to determine and assess the factors and degree of risk of infections by the virus. Data showed that there was significant association between Nipah virus infection and performing activities involving close contact with pigs, such as processing of piglets, administering injection or medication to pigs, assisting in the birth of piglets, assisting in pig breeding, and handling of dead pigs in the affected farms. A complex process of anthropogenic driven deforestation, climatic changes brought on by El Niño-related drought, forest fire and severe haze, and ecological factors of mixed agro-pig farming practices and design of pig-sties led to the spillovers of the virus from its wildlife reservoir into pig population.
    Matched MeSH terms: Disease Outbreaks/prevention & control*
  10. Wong LP, Sam IC
    J Behav Med, 2011 Feb;34(1):23-31.
    PMID: 20680674 DOI: 10.1007/s10865-010-9283-7
    In the setting of the new A(H1N1) outbreak, the study was conducted to assess: (1) fear of the A(H1N1) pandemic; (2) risk avoidance behavior; (3) health-protective behavior; and (4) psychosocial impact in the ethnically diverse population of Malaysia. A cross-sectional, computer-assisted telephone interview was conducted between July 11 and September 12, 2009. A total of 1,050 respondents were interviewed. Fear about the pandemic was high, with 73.2% of respondents reporting themselves as Slightly fearful/Fearful. High risk avoidance and health protective behavior were reported, with 78.0 and 99.0% reporting at least one avoidance and protective behavior respectively. Knowledge was a significant predictor for practice of healthprotective behavior across the three ethnic groups. Level of fear was significantly correlated with number of protective and avoidance behaviors. The study highlights the need for provision of accurate information that increases risk avoidance and health protective behaviors, while at the same time decreases fear or panic in the general public.
    Matched MeSH terms: Disease Outbreaks*
  11. Win MK, Chow A, Chen M, Lau YF, Ooi EE, Leo YS
    Ann Acad Med Singap, 2010 Jun;39(6):448-52.
    PMID: 20625620
    INTRODUCTION: Outbreaks of acute respiratory illness occur commonly in long-term care facilities (LTCF), due to the close proximity of residents. Most influenza outbreak reports have been from temperate countries. This study reports an outbreak of influenza B among a highly immunised resident population in a welfare home in tropical Singapore, and discusses vaccine efficacy and the role of acute respiratory illness surveillance for outbreak prevention and control.

    MATERIALS AND METHODS: During the period from 16 to 21 March 2007, outbreak investigations and active case finding were carried out among residents and nursing staff at the welfare home. Interviews and medical notes review were conducted to obtain epidemiological and clinical data. Hospitalised patients were tested for respiratory pathogens. Further genetic studies were also carried out on positive respiratory samples.

    RESULTS: The overall clinical attack rate was 9.4% (17/180) in residents and 6.7% (2/30) in staff. All infected residents and staff had received influenza immunisation. Fifteen residents were hospitalised, with 2 developing severe complications. Genetic sequencing revealed that the outbreak strain had an 8.2% amino acid difference from B/Malaysia/2506/2004, the 2006 southern hemisphere influenza vaccine strain, which the residents and staff had earlier received.

    CONCLUSIONS: A mismatch between the vaccine and circulating influenza virus strains can result in an outbreak in a highly immunised LTCF resident population. Active surveillance for acute respiratory illness in LTCFs could be implemented for rapid detection of antigenic drift. Enhanced infection control and other preventive measures can then be deployed in a timely manner to mitigate the effect of any outbreaks.

    Matched MeSH terms: Disease Outbreaks/prevention & control*
  12. Tee SF, Chow TJ, Tang PY, Loh HC
    Genet. Mol. Res., 2010;9(3):1274-8.
    PMID: 20623453 DOI: 10.4238/vol9-3gmr789
    The serotoninergic system has been implicated in the etiology of schizophrenia and other behavioral disorders. Association studies have focused on the tryptophan hydroxylase 2 gene (TPH2) and the 5-hydroxytryptamine receptor 2A gene (5-HTR2A). We genotyped two single-nucleotide polymorphisms, A1438G of 5-HTR2A and intronic rs1386494 of TPH2 in the Malay population, using a sample size of 289 schizophrenic patients and 130 healthy controls. We found a significant association of A1438G of 5-HTR2A with schizophrenia in Malays. On the other hand, TPH2 polymorphism was not associated with schizophrenia. This is the first genetic association study concerning schizophrenia in the Malay population.
    Matched MeSH terms: Genetic Predisposition to Disease*
  13. Wong LP, Sam IC
    Prev Med, 2010 Jul;51(1):92-3.
    PMID: 20403375 DOI: 10.1016/j.ypmed.2010.04.010
    This paper aimed to examine the temporal changes in psychobehavioral responses in relation to reported 2009 H1N1 influenza deaths.
    Matched MeSH terms: Disease Outbreaks*
  14. Aizat AA, Shahpudin SN, Mustapha MA, Zakaria Z, Sidek AS, Abu Hassan MR, et al.
    Asian Pac J Cancer Prev, 2011;12(11):2909-13.
    PMID: 22393962
    BACKGROUND: Colorectal cancer (CRC) results from the interaction between environmental exposures and genetic predisposition factors.

    AIMS: A case control study was designed and to investigate the genotype frequencies of P53Arg72Pro polymorphism in Malaysian CRC patients and healthy controls and to determine the associated risk of this polymorphism with CRC predisposition.

    METHODS: In this case-control study, peripheral blood samples of 202 sporadic CRC patients and 201 normal controls were collected, DNA extracted and genotyped using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) technique.

    RESULTS: Genotype analysis showed the frequency of homozygous variant (Pro/Pro) genotype (21%) to be significantly higher in cases compared to controls (13%), (p=0.013). On examining the association between variant genotypes and CRC risk, the Pro/Pro homozygous variant genotype showed significantly higher risk association with CRC susceptibility (OR: 2.047, CI: 1.063-4.044, p=0.033). When stratified according to age, we observed that, individuals aged above 50 years and carriers of pro/pro genotype had significantly higher risk with OR: 3.642, CI: 1.166-11.378, p=0.026.

    CONCLUSIONS: Our results suggest that the codon 72 SNP which results in amino acid substitution of Arginine to Proline in cell cycle regulatory gene P53, is associated with sporadic CRC risk and carriers of Pro/Pro genotype and more than 50 years old may have high susceptibility.
    Matched MeSH terms: Genetic Predisposition to Disease*
  15. Naidu R, Har YC, Taib NA
    Pathol. Int., 2010 Sep;60(9):614-20.
    PMID: 20712647 DOI: 10.1111/j.1440-1827.2010.02568.x
    The aim of the present study was to evaluate the association between the Glyoxalase I (GLOI) Ala111Glu polymorphism and breast cancer risk among the major Malaysian ethnic groups, the Malays, Chinese and Indians, as well as clinico-pathological characteristics of these patients. Genotyping of GLOI gene was performed on blood samples obtained from 387 patients and 252 normal healthy women who had no history of any malignancy using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of GLOI polymorphism were not significantly different between the patients and normal individuals among the Malays (P= 0.721, 0.402), Chinese (P= 0.208, 0.079) and Indians (P= 0.612, 0.349), respectively. The Malay, Chinese and Indian women who were Glu/Glu homozygotes (P= 0.419, 0.093, 0.367), Ala/Glu heterozygotes (P= 0.648, 0.182, 0.402) and carriers of Glu allele (P= 0.402, 0.079, 0.349), respectively, were not associated with breast cancer risk. The Glu allele genotype was significantly associated with absence of progesterone receptor (P= 0.036). Thus, the polymorphic variant of the GLOI gene might not be a useful genetic marker to identify Malaysian Malay, Chinese or Indian women who could be at greater risk of developing breast cancer.

    Study site: Universiti Malaya Medical Centre (UMMC)
    Matched MeSH terms: Genetic Predisposition to Disease/genetics
  16. Saini R, Khim TP, Rahman SA, Ismail M, Tang TH
    Virol J, 2010;7:131.
    PMID: 20550718 DOI: 10.1186/1743-422X-7-131
    Association of High-risk Human Papillomavirus (HR-HPV) with oral cancer has been established recently. Detecting these viruses in oral cavity is important to prevent oral lesions related to them. The purpose of this study was to evaluate the prevalence of HR-HPV in the oral cavity of women with cervical cancer, and their children. A total of 70 women, previously diagnosed with cervical cancer, and 46 children of these women, born by vaginal delivery only, were selected for this study. Buccal swabs were collected from their oral cavity and HPV detection was carried out using Hybrid Capture 2 high-risk HPV (HC2 HR-HPV) detection system.
    Matched MeSH terms: Infectious Disease Transmission, Vertical*
  17. Sam IC, Chan YF, Chan SY, Loong SK, Chin HK, Hooi PS, et al.
    J Clin Virol, 2009 Oct;46(2):180-3.
    PMID: 19683467 DOI: 10.1016/j.jcv.2009.07.016
    BACKGROUND: Chikungunya virus (CHIKV) of the Central/East African genotype has caused large outbreaks worldwide in recent years. In Malaysia, limited CHIKV outbreaks of the endemic Asian and imported Central/East African genotypes were reported in 1998 and 2006. Since April 2008, an unprecedented nationwide outbreak has affected Malaysia.
    OBJECTIVE: To study the molecular epidemiology of the current Malaysian CHIKV outbreak, and to evaluate cross-neutralisation activity of serum from infected patients against isolates of Asian and Central/East African genotypes.
    STUDY DESIGN: Serum samples were collected from 83 patients presenting in 2008, and tested with PCR for the E1 gene, virus isolation, and for IgM. Phylogenetic analysis was performed on partial E1 gene sequences of 837bp length. Convalescent serum from the current outbreak and Bagan Panchor outbreak (Asian genotype, 2006) were tested for cross-neutralising activity against representative strains from each outbreak.
    RESULTS: CHIKV was confirmed in 34 patients (41.0%). The current outbreak strain has the A226V mutation in the E1 structural protein, and grouped with Central/East African isolates from recent global outbreaks. Serum cross-neutralisation activity against both Central/East African and Asian genotypes was observed at titres from 40 to 1280.
    CONCLUSIONS: The CHIKV strain causing the largest Malaysian outbreak is of the Central/East African genotype. The presence of the A226V mutation, which enhances transmissibility of CHIKV by Aedes albopictus, may explain the extensive spread especially in rural areas. Serum cross-neutralisation of different genotypes may aid potential vaccines and limit the effect of future outbreaks.
    Matched MeSH terms: Disease Outbreaks*
  18. Teh CL, Kuan YC, Wong JS
    Rheumatol Int, 2009 Aug;29(10):1243-5.
    PMID: 19373465 DOI: 10.1007/s00296-009-0938-z
    We performed a cross-sectional study of the demography, clinical and laboratory features of patients with systemic sclerosis patients followed up in our centre from 1984 to 2007. There were 23 cases with the majority of them (96%) being female. They have a mean age of 50.3 years and a mean disease duration of 6.02 (SD 5.82) years. Our patients comprised of multi-ethnic groups with predominantly Chinese (52%), Sarawak natives (35%) and Malays (13%). They have a mean lag time to diagnosis of 24.8 (SD 34.8) months. All the patients have sclerodermatous skin changes with 16(70%) having diffuse scleroderma and 7(30%) having limited scleroderma. The common clinical manifestations found in our patients were Raynaud's phenomenon (91%), sclerodactyly (65%), digital ulcers (52%) and pulmonary fibrosis (52%). There was low incidence of pulmonary hypertension (13%) and renal involvement (4%). The majority of our patients (67%) have positive ANA with 33% positive Scl-70. The majority received calcium channel blockers (87%), aspirin (48%) and low-dose prednisolone (48%). One patient developed adenocarcinoma of the lung on follow-up. This study demonstrated the rarity of systemic sclerosis in our centre with considerable lag time to diagnosis in our patients. Diffuse cutaneous systemic scleroderma is more common in our centre with rare pulmonary hypertension and renal involvement.
    Matched MeSH terms: Raynaud Disease/diagnosis*
  19. Mannerås L, Fazliana M, Wan Nazaimoon WM, Lönn M, Gu HF, Ostenson CG, et al.
    J Ethnopharmacol, 2010 Feb 3;127(2):346-51.
    PMID: 19883744 DOI: 10.1016/j.jep.2009.10.032
    New options are needed to prevent and treat metabolic disorders associated with polycystic ovary syndrome (PCOS). Labisia pumila var. alata (LPva)-a Malaysian herb thought to have phytoestrogenic effects-has shown promise in reducing body weight gain in ovariectomized rats. In this study, we investigated the effect of LPva on body composition and metabolic features in female rats treated continuously with dihydrotestosterone, starting before puberty, to induce PCOS.
    Matched MeSH terms: Disease Models, Animal*
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