Displaying publications 21 - 40 of 52 in total

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  1. Rajendra S, Ackroyd R, Murad S, Mohan C, Ho JJ, Goh KL, et al.
    Aliment Pharmacol Ther, 2005 Jun 1;21(11):1377-83.
    PMID: 15932368
    Characteristic immune profiles have been demonstrated in gastro-oesophageal reflux disease. However, the genetic basis of gastro-oesophageal reflux disease remains unclear.
  2. Gendeh BS, Murad S, Razi AM, Abdullah N, Mohamed AS, Kadir KA
    Otolaryngol Head Neck Surg, 2000 May;122(5):758-62.
    PMID: 10793361
    The aim of the study was to determine the incidence of food and house dust mite (HDM) allergy in patients with nasal congestion and rhinorrhea attending the Otorhinolaryngology Clinic, National University of Malaysia, Kuala Lumpur. This was a prospective matched, controlled study of patients skin prick tested with commercial food and common aeroallergens. The participants were 148 Malaysian adults with symptoms of nasal congestion and rhinorrhea and 113 adult Malaysian control subjects without rhinitis symptoms. The skin prick test (SPT) was used to evaluate 11 foods common to the Malaysian diet and 3 HDM inhalants. Forty-eight percent of the patients with rhinitis had positive SPT results to foods, compared with 4.4% of control subjects (P < 0.05). The most commonly implicated foods were shrimp (48%) and rice (30%), which are common in the Malaysian diet. Seventy-two percent of rhinitis patients had positive SPT results to HDM, compared with 22.2% of control subjects (P < 0.05). Patients with rhinitis also had significantly more gastrointestinal problems than control subjects (P < 0.05). The incidences of HDM and food allergy are significantly greater in Malaysian adults with rhinitis symptoms than in control subjects without rhinitis. The effect of avoidance or immunotherapy awaits further study.
    Study site: Otorhinolaryngology Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
  3. Chun-Lai T, Murad S, Erlandsson MC, Hussein H, Sulaiman W, Dhaliwal JS, et al.
    Medicine (Baltimore), 2015 Jan;94(4):e468.
    PMID: 25634192 DOI: 10.1097/MD.0000000000000468
    Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n = 1233) and controls (n = 1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR = 5.40, 95% CI 3.81-7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR = 16.21, 95% CI 5.70-46.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.
  4. Mohamad Yadzir ZH, Bakhtiar F, Misnan R, Abdullah N, Leecyous B, Murad S
    Iran J Allergy Asthma Immunol, 2016 Apr;15(2):156-60.
    PMID: 27090369
    Allergy diagnosis needs to be improved in polysensitized patients due to the existence of possible confounding factors in this type of patients. Component resolved diagnosis (CRD) is a new concept in the investigation of polysensitized patients. The aim of this study was to evaluate if the utilization of ImmunoCAP ISAC improve the diagnosis of the polysensitized allergic rhinitis patients. Skin prick test (SPT) to 58 crude allergen extracts and CRD (ImmunoCAP ISAC) were carried out for 5 polysensitized allergic rhinitis patients. Two patients had a shellfish allergy and avoidance of shellfish was the only way to prevent an allergic reaction. In contrast, although the remaining three patients had low risk for shellfish allergy, but they were the best candidates for immunotherapy using mite extracts. CRD and particularly ImmunoCAP ISAC have proven to be a valuable diagnostic tool in polysensitized patients. ImmunoCAP ISAC helps refine the individual patient's sensitization profile and predict the potential risk of allergic reactions and improve the selection of patients for immunotherapy.
  5. Mohamad Yadzir ZH, Misnan R, Abdullah N, Bakhtiar F, Leecyous B, Murad S
    Iran J Allergy Asthma Immunol, 2014 Aug;13(4):240-6.
    PMID: 24659159
    Component-resolved diagnosis (CRD) using microarray technology has recently been introduced with the aim to improve diagnosis of allergy. The aim of this study was to compare performance of this allergen microarray to those of an established extract-based skin prick testing (SPT).45 patients with allergic rhinitis were studied (16 children and 29 adults). SPT to Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis extracts and allergen microarray ImmunoCAP ISAC were carried out for all patients. Forty out of 45 patients demonstrated positive SPT to all mite extracts tested. These 40 patients were considered to be mite-allergic based on the positive SPT results. The remaining 5 patients with negative SPT to any mite extracts were classified as non-mite allergic. Comparatively, based on the microarray results, only 34 mite-allergic patients had detectable serum IgE to at least one of the mite allergen components tested whereas 6 patients with positive SPT to mite extracts showed no detectable IgE reactivity to any of the components tested. One non-mite allergic patient had a positive test- Blo t 5. Der p 10-positive patients also reacted to other cross-reactive tropomyosin from anisakis (Ani s 3) (25%), cockroach (Bla g 7) (50%) and shrimp (Pen m 1) (75%). CRD is a reliable tool for the diagnosis of allergy to mites. Der p 10 might be a useful indicator to identify a subset of mite-allergic patient that have additional sensitization due to cross-reactivity and thus allows selection of patients for immunotherapy.
  6. Misnan R, Salahudin Abd Aziz N, Mohamad Yadzir ZH, Bakhtiar F, Abdullah N, Murad S
    Iran J Allergy Asthma Immunol, 2016 Aug;15(4):309-316.
    PMID: 27921412
    Snail is one of the worst causes of food allergy. Thus, the aim of this study was to identify the major and minor allergens of the local marine snail (Cerithidea obtusa) and subsequently to investigate the impacts of heat treatment on the IgE-binding activity of snail allergens. Proteins from raw and heat-treated snails (boiled, roasted and fried) were extracted and then resolved by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Immunoblotting of all extracts were then performed using sera from patients with snail allergy. The results showed that the raw extract contains numerous protein bands between 12 to>250 kDa. Some thermostable proteins, predominantly the 33 and 42 kDa bands, remained detected in all cooked extracts with decreasing intensities from boiled to roasted to fried extracts, while the majority of thermolabile bands denatured after heating. Boiled snail had more protein bands compared to roasted and fried snails. Immunoblotting of raw extract demostrated 19 IgE-binding bands ranging from 15 to 240 kDa. The thermostable bands of 33 and 42 kDa and a thermolabile of 30 kDa band were identified as the major allergens of this snail. The cooked extracts yielded less allergenic bands. The boiled extract yielded approximately 14 IgE-binding bands with some smeared bands at high molecular weight regions. The roasted extract had lesser IgE-binding bands and the majority appeared as smears, while the IgE-reactivity in the fried extract was less visible and appeared as weak smears. This study indicated that both raw and cooked snails played a crucial role in snail allergenicity, as this species of snail contains both thermostable and thermolabile major allergens. The degree of snail allergenicity was revealed in the order: raw> boiled > roasted> fried. Thus, the results would facilitate in the development of effective diagnosis and management strategies of snail allergy in this country.
  7. Too CL, Murad S, Dhaliwal JS, Larsson P, Jiang X, Ding B, et al.
    Arthritis Res Ther, 2012;14(6):R250.
    PMID: 23164236 DOI: 10.1186/ar4093
    INTRODUCTION: The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations.
    METHODS: A total of 320 SNPs from the PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations.
    RESULTS: The overall odds ratio (ORoverall) for the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a protective effect (P = 0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising 5,192 RA cases and 4,317 control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08) and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)).
    CONCLUSION: Our study demonstrates an association between PADI4 and RA in the multiethnic population from South East Asia and suggests additional association with a PADI2 gene. The study thus provides further support for the notion that polymorphisms in genes for enzymes responsible for citrullination contribute to RA development in multiple populations of Asian descent.
  8. Too CL, Muhamad NA, Ilar A, Padyukov L, Alfredsson L, Klareskog L, et al.
    Ann Rheum Dis, 2016 06;75(6):997-1002.
    PMID: 26681695 DOI: 10.1136/annrheumdis-2015-208278
    OBJECTIVES: Lung exposures including cigarette smoking and silica exposure are associated with the risk of rheumatoid arthritis (RA). We investigated the association between textile dust exposure and the risk of RA in the Malaysian population, with a focus on women who rarely smoke.

    METHODS: Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis population-based case-control study involving 910 female early RA cases and 910 female age-matched controls were analysed. Self-reported information on ever/never occupationally exposed to textile dust was used to estimate the risk of developing anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. Interaction between textile dust and the human leucocyte antigen DR β-1 (HLA-DRB1) shared epitope (SE) was evaluated by calculating the attributable proportion due to interaction (AP), with 95% CI.

    RESULTS: Occupational exposure to textile dust was significantly associated with an increased risk of developing RA in the Malaysian female population (OR 2.8, 95% CI 1.6 to 5.2). The association between occupational exposure to textile dust and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.3 to 4.8) and ACPA-negative RA (OR 3.5, 95% CI 1.7 to 7.0) subsets, respectively. We observed a significant interaction between exposure to occupational textile dust and HLA-DRB1 SE alleles regarding the risk of ACPA-positive RA (OR for double exposed: 39.1, 95% CI 5.1 to 297.5; AP: 0.8, 95% CI 0.5 to 1.2).

    CONCLUSIONS: This is the first study demonstrating that textile dust exposure is associated with an increased risk for RA. In addition, a gene-environment interaction between HLA-DRB1 SE and textile dust exposure provides a high risk for ACPA-positive RA.
  9. Yadzir ZH, Misnan R, Abdullah N, Bakhtiar F, Arip M, Murad S
    Asian Pac J Trop Biomed, 2012 Jan;2(1):50-4.
    PMID: 23569834 DOI: 10.1016/S2221-1691(11)60189-5
    OBJECTIVE: To characterize the major allergens of Macrobrachium rosenbergii (giant freshwater prawn).

    METHODS: Raw and cooked extracts of the giant freshwater prawn were prepared. The IgE reactivity pattern was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting technique with the sera of 20 skin prick test (SPT) positive patients. The major allergen identified was then characterized using the proteomics approach involving a combination of two-dimensional (2-DE) electrophoresis, mass spectrometry and bioinformatics tools.

    RESULTS: SDS-PAGE of the raw extract showed 23 protein bands (15-250 kDa) but those ranging from 40 to 100 kDa were not found in the cooked extract. From immunoblotting experiments, raw and cooked extracts demonstrated 11 and 5 IgE-binding proteins, respectively, with a molecular mass ranging from 15 to 155 kDa. A heat-resistant 36 kDa protein was identified as the major allergen of both extracts. In addition, a 42 kDa heat-sensitive protein was shown to be a major allergen of the raw extract. The 2-DE gel fractionated the prawn proteins to more than 50 different protein spots. Of these, 10 spots showed specific IgE reactivity with patients' sera. Matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis led to identification of 2 important allergens, tropomyosin and arginine kinase.

    CONCLUSIONS: It can be concluded that the availability of such allergens would help in component-based diagnosis and therapy of prawn allergies.

  10. Lee HL, Vasan S, Ahmad NW, Idris I, Hanum N, Selvi S, et al.
    Transgenic Res, 2013 Feb;22(1):47-57.
    PMID: 22700207 DOI: 10.1007/s11248-012-9625-z
    We conducted the world's first experiments under semi-field conditions (ACL-2 field house) to assess the mating competitiveness of genetically sterile RIDL male mosquitoes (513A strain). The field house is a state-of-the-art, fully-contained trial facility, simulating the living space for a household of 2-4 people in Peninsular Malaysia. Ten genetically sterile RIDL male A. aegypti mosquitoes competed with ten wild type males inside this field house to mate with ten wild type females. Hatched larvae from mated females were screened under a fluorescent microscope for genetic markers to determine if they were fathered by RIDL male or wild type male, and all results were cross-checked by PCR. Two such experiments were conducted, each repeated sufficient number of times. All strains were on a Malaysian lab strain background for the first experiment, while the RIDL males alone were on a recently-colonised Mexican strain background for the second experiment. A total of 52 % of the matings were with RIDL males in the first experiment, while 45 % of the matings were with RIDL (Mexican) males in the second experiment. Statistically, this is not significantly different from 50 % of the matings expected to take place with RIDL males if the latter were as competitive as that of the wild type males. This shows that A. aegypti RIDL-513A has excellent mating competitiveness under semi-field conditions, verifying earlier trends obtained in small lab cages. We also observed high mating compatibility between recently-colonised Mexican RIDL males and lab-reared Malaysian wild type females.
  11. Sahabudin S, Misnan R, Yadzir ZH, Mohamad J, Abdullah N, Bakhtiar F, et al.
    Malays J Med Sci, 2011 Jul;18(3):27-32.
    PMID: 22135598 MyJurnal
    BACKGROUND: Prawns and shrimp are a frequent cause of seafood allergy mediated by IgE antibodies. Penaeus monodon and Penaeus latisulcatus, commonly known as black tiger prawn and king prawn, respectively, are among the most frequently consumed prawns in Malaysia. The aim of this study was to identify the IgE-binding proteins of these 2 prawn species.
    METHODS: Raw and boiled prawn extracts were prepared and then resolved by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). IgE-immunoblotting was then performed using sera from patients with positive skin prick tests to the raw prawn extracts.
    RESULTS: SDS-PAGE analysis of the raw extracts of both prawn species revealed 23 protein bands; the boiled extracts yielded fewer protein bands. The bands in the range of 40 to 100 kDa were sensitive to heat and therefore were not found in the boiled extracts. Immunoblot of raw extracts of black tiger prawns and king prawns yielded 14 and 11 IgE-binding proteins, respectively, with molecular weights of between 15 and 200 kDa. Proteins at 36, 42, and 49 kDa were detected as the major allergens in both species of prawns. A protein of 75 kDa was also identified as a major allergen in black tiger prawns. Other potential allergens were also observed at various molecular masses.
    CONCLUSION: Proteins of 36, 42, and 49 kDa were identified as the major allergens of both species of prawns. The 36 and 42 kDa proteins are hypothesised to be tropomyosin and arginine kinase, respectively. A high molecular weight protein of 75 kDa was found to be an additional major allergen in black tiger prawns.
    KEYWORDS: Penaeus; allergens; allergy and clinical immunology; hypersensitivity; immunoblotting; tropomyosin
  12. Yahya A, Bengtsson C, Larsson P, Too CL, Mustafa AN, Abdullah NA, et al.
    Mod Rheumatol, 2014 Mar;24(2):271-4.
    PMID: 24593203 DOI: 10.3109/14397595.2013.854076
    OBJECTIVES: Silica exposure has been associated with an increased risk of developing rheumatoid arthritis (RA), especially among smokers. In this study, we aimed at examining the association between silica exposure (and its interaction with smoking) and the risk of RA in the Malaysian population.
    METHODS: In total, 149 cases and 213 matched controls, all men, were included between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched on sex, age and residential area. Silica exposure was defined as exposure to stone dust, rock drilling or stone crushing, and smoking status was categorized as ever/never cigarette smoking.
    RESULTS: An increased risk of anti-citrullinated protein antibody (ACPA)-positive RA (OR = 2.4, 95 % CI 1.0-5.6) was observed among those exposed to silica. Ever-smokers exposed to silica had a particularly high risk of developing ACPA-positive RA (OR = 7.5, 95 % CI 2.3-24.2), compared with never-smokers not exposed to silica. No association was found regarding ACPA-negative RA.
    CONCLUSION: Our data demonstrate that exposure to both silica and cigarette smoke comprise risks for developing RA in the Malaysian genetic context. The findings expand a link between environmental lung exposures and ACPA-positive RA to Asian populations.
  13. Guo J, Wu X, Too CL, Yin F, Lu X, He J, et al.
    PLoS One, 2012;7(7):e41228.
    PMID: 22829930 DOI: 10.1371/journal.pone.0041228
    OBJECTIVES: Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.

    METHODS: We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.

    RESULTS: DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall) =1.17, 95% CI 1.06-1.30, P=0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis).

    CONCLUSIONS: Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.
  14. Yahya A, Bengtsson C, Lai TC, Larsson PT, Mustafa AN, Abdullah NA, et al.
    Mod Rheumatol, 2012 Aug;22(4):524-31.
    PMID: 22006120 DOI: 10.1007/s10165-011-0544-2
    We investigated the association between cigarette smoking and the risk of developing rheumatoid arthritis (RA) in the Malaysian population. A total of 1,056 RA patients and 1,416 matched controls aged 18-70 years within a defined area of Peninsular Malaysia were evaluated in a case-control study between August 2005 and December 2009. A case was defined as a person with early diagnosed RA using the 1987 American College of Rheumatology criteria for RA. Controls were randomly selected matched for sex, age, and residential area. Cases and controls answered a questionnaire on a broad range of issues, including lifestyle factors and smoking habits wherein current and former smoking was classified as ever-smoking. The presence of anti-citrullinated peptide antibodies (ACPA) was determined for cases and controls. We found that ever-smokers had an increased risk of developing ACPA-positive RA [odds ratio (OR) = 4.1, 95% confidence interval (CI) 1.9-9.2] but not ACPA-negative RA (OR = 0.7, 95% CI 0.3-2.0), compared with never-smokers. A significant dose-response relationship between cumulative dose of smoking and risk of ACPA-positive RA was observed (<20 pack-years OR = 3.3, 95% CI 1.1-9.8; at least 20 pack-years OR = 5.2, 95% CI 1.6-17.6). Hence, smoking is associated with an increased risk of ACPA-positive RA in the Malaysian population, in which the genetic context is similar to several other Asian countries.
  15. Gill HK, Kumar HC, Dhaliwal JS, Zabidi F, Sendut IH, Noah RM, et al.
    Asian Pac J Allergy Immunol, 2012 Dec;30(4):313-20.
    PMID: 23393912
    BACKGROUND: The most common autosomal form of Chronic Granulomatous Disease, p47-phox deficient CGD, generally features a GT (deltaGT) deletion in the GTGT sequence at the start of exon 2 on the NCF-1 gene. This consistency is due to the coexistence of and the recombination between 2 homologous pseudogenes (psi s) and NCF-1. The GTGT: deltaGT ratio mirrors the NCF-I: NCF-1 psi ratio and is 2:4 in normal individuals.
    OBJECTIVE: To determine the molecular basis of the Autosomal-CGD in a family with 2 children, a male and female, affected by the disease. The female patient suffered recurrent infection, retinitis pigmentosa and discoid lupus.
    METHODS: Chemiluminescence (CL) was used to study the respiratory burst, while genetic analysis was done by RT-PCR, PCR, deltaGT and the 20bp gene scans.
    RESULTS: The CL response of the patient was profoundly low. The patient's p47-phox band was absent in the RT-PCR for NADPH-oxidase component mRNAs. The deltaGT scan showed that the patient's GTGT: deltaGT ratio was 0:6, the parents' and the younger brother's was 1:5 and the younger sister's was 2:4. Examination of other NCF-1/ NCF-1 psi s differences showed that the father had a compound deltaGT allele ie. deltaGT-20bp, inherited by the patient, and that both parents had compound GTGT alleles with a single 30bp segment in intron 1.
    CONCLUSIONS: The patient was a classic, homozygous deltaGT p47-phox deficient CGD with one allele harbouring a compound deltaGT-20bp gene. The deltaGT and 20bp gene scans offer a relatively simple and efficient means of defining a p47-phox deficient CGD patient.
    Key words: Chronic Granulomatous Disease, Primary Immunodeficiency, NCF-1, p47-phox, NADPH-oxidas
  16. Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung WH, et al.
    Pharmacogenomics J, 2017 03;17(2):170-173.
    PMID: 26927288 DOI: 10.1038/tpj.2016.10
    Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.
  17. Bakhtiar MF, Too CL, Tang MM, Sulaiman S, Tan LK, Ahmad-Fauzi NA, et al.
    Clin Exp Allergy, 2019 04;49(4):537-540.
    PMID: 30693574 DOI: 10.1111/cea.13347
  18. Muhamad NA, Buang SN, Jaafar S, Jais R, Tan PS, Mustapha N, et al.
    BMC Public Health, 2018 Dec 22;18(1):1402.
    PMID: 30577816 DOI: 10.1186/s12889-018-6316-6
    BACKGROUND: In 2006, 4 years of planning was started by the Ministry of Health, Malaysia (MOH), to implement the HPV (human papillomavirus) vaccination programme. An inter-agency and multi-sectoral collaborations were developed for Malaysia's HPV school-based immunisation programme. It was approved for nationwide school base implementation for 13-year-old girls or first year secondary students in 2010. This paper examines how the various strategies used in the implementation over the last 7 years (2010-2016) that unique to Malaysia were successful in achieving optimal coverage of the target population.

    METHODS: Free vaccination was offered to school girls in secondary school (year seven) in Malaysia, which is usually at the age of 13 in the index year. All recipients of the HPV vaccine were identified through school enrolments obtained from education departments from each district in Malaysia. A total of 242,638 girls aged between 12 to 13 years studying in year seven were approached during the launch of the program in 2010. Approximately 230,000 girls in secondary schools were offered HPV vaccine per year by 646 school health teams throughout the country from 2010 to 2016.

    RESULTS: Parental consent for their daughters to receive HPV vaccination at school was very high at 96-98% per year of the programme. Of those who provided consent, over 99% received the first dose each year and 98-99% completed the course per year. Estimated population coverage for the full vaccine course, considering also those not in school, is estimated at 83 to 91% per year. Rates of adverse events reports following HPV vaccination were low at around 2 per 100,000 and the majority was injection site reactions.

    CONCLUSION: A multisectoral and integrated collaborative structure and process ensured that the Malaysia school-based HPV immunisation programme was successful and sustained through the programme design, planning, implementation and monitoring and evaluation. This is a critical factor contributing to the success and sustainability of the school-based HPV immunisation programme with very high coverage.

  19. Low DE, Nurul-Aain AF, Tan WC, Tang JJ, Bakhtiar MF, Murad S, et al.
    Pharmacogenet Genomics, 2020 09;30(7):153-160.
    PMID: 32433341 DOI: 10.1097/FPC.0000000000000408
    OBJECTIVE: The association between human leukocyte antigen (HLA)-B*58:01 and risk of allopurinol-induced severe cutaneous adverse reactions (AIS) was observed across different populations. We explore the association between HLA-B*58:01 and AIS risk in multiethnic Malaysian population. The HLA-B*58:01 risk for different AIS clinical phenotypes and ethnicity was determined.

    METHODS: We performed a case-control association study by genotyping the HLA-B alleles of 55 patients with AIS [11 toxic epidermal necrolysis (TEN), 21 Steven Johnson syndrome (SJS) 22 drug reaction wit eosinophilia and systemic symptoms (DRESS) and one acute generalized exanthematous pustulosis (AGEP)] and 42 allopurinol-tolerant controls (ATC).

    RESULTS: HLA-B*58:01 was positive in 89.1 and 14.3% of the AIS and ATC study groups [odds ratio (OR) = 49.0, 95% confidence interval (CI) = 14.6-164.4, P < 0.0001)], respectively. Our data showed that 93.8% of the AIS-SJS/TEN patients and 86.4% of the AIS-DRESS patients were HLA-B*58:01 positive (AIS-SJS/TEN, OR = 90, 95% CI = 16.9-470.1, P < 0.0001 and AIS-DRESS OR = 38, 95% CI = 8.5-169.2, P < 0.0001). Stratification by ethnicity and clinical phenotypes revealed a significant increased risk between HLA-B*58:01 and Chinese-AIS patients (OR = 137.5, 95% CI = 11.3-1680.2, P < 0.0001), in particular Chinese patients with AIS-SJS/TEN phenotype (100% HLA-B*58:01 positive). HLA-B*58:01 was positive in 90.9% Chinese AIS-DRESS (P < 0.0001). Highly significant associations of HLA-B*58:01 were observed in Malay AIS-SJS/TEN (OR = 78, 95% CI = 9.8-619.9, P < 0.0001) and Malay AIS-DRESS (OR = 54, 95% CI = 6.6-442.9, P < 0.0001). Although the number of Indian-AIS patients was relatively small (n = 2), both were HLA-B*58:01 positive.

    CONCLUSION: Our data suggest strong associations between HLA-B*58:01 and AIS in Malaysian population with Chinese and Malays ethnicity. The strong association was also observed in three different clinical phenotypes of AIS, mainly the AIS-SJS/TEN.

  20. Too CL, Murad S, Hansson M, Alm LM, Dhaliwal JS, Holmdahl R, et al.
    Arthritis Rheumatol, 2017 01;69(1):58-69.
    PMID: 27483449 DOI: 10.1002/art.39827
    OBJECTIVE: Antibodies to the citrullinated protein antigens (ACPAs) are important in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the prevalence of ACPAs with different fine specificities in different populations is unclear. This study sought to examine the fine specificity of the antibody responses toward citrullinated proteins in RA patients from Malaysia, an area where genetic and environmental determinants of RA are different from those in more frequently studied cohorts of Caucasian subjects.

    METHODS: A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17, Vim60-75], fibrinogen [Fibα563-583, Fibα580-600, Fibβ36-52, Fibβ62-81a, Fibβ62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%.

    RESULTS: Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60-75, Vim2-17, Fibβ62-81b, Eno5-21, and CitCII355-378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti-cyclic citrullinated peptide 2 antibodies. In Malaysian RA patients compared with Swedish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%, corrected P [Pcorr ] = 1.06 × 10-8 ) and CitCII355-378 (17% versus 13%, Pcorr  = 0.02) were significantly higher, while the frequencies of antibodies to Vim2-17 (25% versus 32%, Pcorr  = 1.91 × 10-4 ), Fibβ62-81b (15% versus 30%, Pcorr  = 2.47 × 10-22 ), and Eno5-21 (23% versus 50%, Pcorr  = 3.64 × 10-57 ) were significantly lower.

    CONCLUSION: Serum ACPA fine specificities differ between RA patients in different populations, although the total proportions of individuals positive for ACPAs are similar. Differing patterns of ACPA fine specificity could be attributed to variations in genetic and/or environmental factors.

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