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A new HLA-B*35 allele, B*3589, detected in a Malaysian individual

Phipps M, Jinam T

Tissue Antigens, 2009 Mar;73(3):279-80.
PMID: 19144089 DOI: 10.1111/j.1399-0039.2008.01195.x

A novel human leukocyte antigen-B allele officially named B*3589, was found in an indigenous individual of Jehai ethnicity when sequencing was performed to investigate human genome variation in a research project. B*3589 differs form B*3505 in a point mutation at codon 169 (CGC to TGC) resulting in an amino acid change from Arg to Cys.
Plasmid incidence rate and conjugative chloramphenicol and tetracycline resistance plasmids in Malaysian isolates of Salmonella typhi

Phipps M, Pang T, Koh CL, Puthucheary S

Microbiol. Immunol., 1991;35(2):157-61.
PMID: 1886492

Seven (6.1%) of 115 strains of Salmonella typhi isolated from Malaysian patients harbored a single large plasmid of 71 to 166 mD. Two of the seven plasmid-bearing strains were resistant to chloramphenicol (Cm) and tetracycline (Tc) and they transferred Cm and Tc resistance traits to Escherichia coli K12 at frequencies from 1.6 x 10(-7) to 1.9 x 10(-6). Agarose gel electrophoresis provided evidence that the resistance traits were cotransferred on a conjugative plasmid. The significance and importance of these results are discussed.
Possible virulence factors involved in bacteraemia caused by Aeromonas hydrophila

Vadivelu J, Puthucheary SD, Phipps M, Chee YW

J Med Microbiol, 1995 Mar;42(3):171-4.
PMID: 7884797

Eighteen strains of Aeromonas hydrophila from patients with bacteraemia were investigated for possible virulence factors. Cytotoxin and haemolysin were produced by all strains, whereas cholera toxin-like factor was produced by 33% of strains only. Enterotoxin production was not detected. Haemagglutination of guinea-pig, fowl and rabbit erythrocytes was demonstrated by 83%, 67% and 61% of strains, respectively. Fucose- and mannose-sensitive haemagglutinins were predominant. None of the strains agglutinated sheep erythrocytes. Extrachromosomal DNA was detected in 17 strains, 16 of which had a plasmid (3.6-5.1 MDa), the majority being between 4.6 and 5.1 MDa.
Molecular analysis of HLA Class I and Class II genes in four indigenous Malaysian populations

Jinam TA, Saitou N, Edo J, Mahmood A, Phipps ME

Tissue Antigens, 2010 Feb;75(2):151-8.
PMID: 20003135 DOI: 10.1111/j.1399-0039.2009.01417.x

This is the first report of high-resolution human leukocyte antigen (HLA) typing in four indigenous groups in Malaysia. A total of 99 normal, healthy participants representing the Negrito (Jehai and Kensiu), Proto-Malay (Temuan) and a native group of Borneo (Bidayuh) were typed for HLA-A, -B, -DRB1 and -DQB1 genes using sequence-based typing. Eleven HLA-A, 26 HLA-B, 16 HLA-DRB1 and 14 HLA-DQB1 alleles were detected, including a new allele, HLA-B*3589 in the Jehai. Highly frequent alleles were A*2407, B*1513, B*1801, DRB1*0901, DRB1*1202, DRB1*1502, DQB1*0303 and DQB1*0502. Principal component analysis based on high-resolution HLA-A, -B and -DRB1 allele frequencies showed close affinities among all four groups, including the Negritos, with other Southeast Asian populations. These results showed the scope of HLA diversity in these indigenous minority groups and may prove beneficial for future disease association, anthropological and forensic studies.
Fulltext VNTR markers for qualitative evaluation of engraftment in unrelated cord blood transplantations

Noor SM, Phipps ME, Fong MY, Chan LL

Med J Malaysia, 2007 Mar;62(1):23-6.
PMID: 17682565 MyJurnal

Allogeneic stem cell transplantation is a treatment option for malignant and non-malignant disorders in children. For children with no HLA-matched sibling or related stem cell donors, there is the option of unrelated cord blood donors. At the University of Malaya Medical Centre (UMMC) in Kuala Lumpur, the first unrelated cord blood transplantation (CBT) was performed in October 1997. All unrelated CBT performed in UMMC relied on cord blood units imported from overseas. DNA typing with variable number of tandem repeat (VNTR) loci was done to qualitatively evaluate engraftment in 15 unrelated CBT. In all the fifteen cases that were evaluated, molecular evidence of engraftment or non-engraftment correlated with the clinical findings.
The distribution of major histocompatibility complex class I polymorphic Alu insertions and their associations with HLA alleles in a Chinese population from Malaysia

Dunn DS, Choy MK, Phipps ME, Kulski JK

Tissue Antigens, 2007 Aug;70(2):136-43.
PMID: 17610418

The frequency and association of polymorphic Alu insertions (POALINs) with human leucocyte antigen (HLA) class I genes within the class I genomic region of the major histocompatibility complex (MHC) have been reported previously for three populations: the Australian Caucasian, Japanese and north-eastern Thai populations. Here, we report on the individual insertion frequency of the five POALINs within the MHC class I region, their HLA-A and HLA-B associations, the POALIN haplotype frequencies and the HLA-A/POALIN four-loci haplotype frequencies in the Malaysian Chinese population. The phylogenetic relationship of the four populations based on the five POALIN allele frequencies was also examined. In the Malaysian Chinese population, the POALIN AluyHG was present at the highest frequency (0.560), followed by AluyHJ (0.300), AluyMICB (0.170), AluyTF (0.040) and AluyHF (0.030). The most frequent five-loci POALIN haplotype of the 16 inferred haplotypes was the AluyHG single insertion haplotype at a frequency of 0.489. Strong associations were present between AluyHJ and HLA-A24, HLA-A33 and HLA-A11 and between AluyHG and HLA-A2, HLA-A24 and HLA-A11, and these were reflected by the inferred haplotype frequencies constructed from the combination of the HLA-A locus and the AluyHG, AluyHJ and AluyHF loci. The strongest association of AluyMICB was with the HLA-B54 allele (five of five), whereas the associations with the other 17 HLA-B alleles were weak, moderate or undetermined. Phylogenetic analysis of the five POALIN allele frequencies places the Malaysian Chinese closest to the Japanese and north-eastern Thai populations in the same cluster and separate to the Australian Caucasian population. The MHC POALINs are confirmed in this study to be informative genetic markers in lineage (haplotype) analysis, population genetics and evolutionary relationships, especially in studying the MHC genomic region.
HLA variants rs9271366 and rs9275328 are associated with systemic lupus erythematosus susceptibility in Malays and Chinese

Chai HC, Phipps ME, Othman I, Tan LP, Chua KH

Lupus, 2013 Feb;22(2):198-204.
PMID: 23257407 DOI: 10.1177/0961203312470183

BACKGROUND: Human leukocyte antigen (HLA) antigens and genes have long been reported associated with systemic lupus erythematosus (SLE) susceptibility in many populations. With the advance in technologies such as genome-wide association studies, many newly discovered SLE-associated single-nucleotide polymorphisms (SNPs) have been reported in recent years. These include HLA-DRB1/HLA-DQA1 rs9271366 and HLA-DQB1/HLA-DQA2 rs9275328. Our aim was to investigate these SNPs in a Malaysian SLE cohort.
MATERIALS AND METHODS: SNPs rs9271366 and rs9275328 were screened across 790 Malaysian citizens from three ethnic groups (360 patients and 430 healthy volunteers) by Taqman SNP genotyping assays. Allele and genotyping frequencies, Hardy-Weinberg equilibrium, Fisher's exact test and odds ratio were calculated for each SNP and ethnic group. Linkage disequilibrium and interaction between the two SNPs were also evaluated.
RESULTS: The minor allele G and its homozygous genotype GG of HLA-DRB1/HLA-DQA1 rs9271366 significantly increased the SLE susceptibility in Malaysian patients, including those of Malay and Chinese ethnicity (odds ratio (OR) > 1, p
Human Fc gamma receptor IIA (FcgammaRIIA) genotyping and association with systemic lupus erythematosus (SLE) in Chinese and Malays in Malaysia

Yap SN, Phipps ME, Manivasagar M, Tan SY, Bosco JJ

Lupus, 1999;8(4):305-10.
PMID: 10413210 DOI: 10.1191/096120399678847876

SLE is an autoimmune and polygenic disorder characterized by an accumulation and deposition of immune complexes. Several studies have indicated differential impact of FcgammaR polymorphism genotypes in different ethnic groups studied. The Fc receptor for IgG class IIA gene (FcgammaRIIA) occurs in two allelic forms. The allele FcgammaRIIA-H131 encodes a receptor with a histidine at the 131 amino acid position; the other allele FcgammaRIIA-R131 encodes an arginine. This polymorphism is believed to determine the affinity of the receptor for hIgG2 in immune complexes. FcgammaRIIA-H131 has a higher capacity for hIgG2 compared to FcgammaRIIA-R131 as measured by in vitro studies of insoluble immune complex clearance. We have investigated the polymorphism for FcgammaRIIA using a novel polymerase chain reaction-allele specific primer (PCR-ASP) method designed specifically to distinguish the two allelic forms. Our studies were based on 175 Chinese and 50 Malays SLE patients as well as 108 and 50 ethnically matched healthy controls for the respective groups. Analysis of the data (chi2 test with Yates correction factors and odds ratios) revealed that there were no significant differences between SLE patients and controls. We have not found evidence of a protective effect conferred by FcgammaRIIA-H131 in the ethnic groups studied.
Fc gamma receptor IIIB-NA gene frequencies in patients with systemic lupus erythematosus and healthy individuals of Malay and Chinese ethnicity

Yap SN, Phipps ME, Manivasagar M, Bosco JJ

Immunol Lett, 1999 Jun 01;68(2-3):295-300.
PMID: 10424435

The neutrophil antigen (NA)1 and 2 is coded by two recognized allelic forms of Fc gamma receptor IIIB (FcgammaRIIIB). FcgammaRIIIb is a low affinity receptor and preferentially removes immune complexes from the circulation. Systemic lupus erythematosus (SLE) is an autoimmune and polygenic disorder characterized by accumulation of autoimmune complexes. The majority of SLE patients in our medical center are of Chinese ethnicity, followed by Malay and Indian. Recently, studies have focussed on the Fc receptors in different ethnic groups and their relation to SLE. We chose to study the gene distribution of this receptor in the Chinese and Malays population in Malaysia. We designed a polymerase chain reaction allele specific primers (PCR-ASP) method to distinguish the two allelic forms. Genomic DNA was isolated from the peripheral blood of 183 Chinese and 55 Malays SLE patients as well as 100 Chinese and 50 Malays healthy controls. Genotyping of Chinese SLE patients revealed that the gene frequencies for FcgammaRIIIB-NA1 and FcgammaRIIIB-NA2 were 0.648 and 0.347, while in the ethnically matched healthy controls they were 0.68 and 0.32, respectively. One out of the 183 Chinese SLE patients was identified as a NA-null due to the absence of PCR product for both alleles. The FcgammaRIIIB-NA1 and FcgammaRIIIB-NA2 allele frequencies for both the Malays SLE and healthy controls were 0.62 and 0.38.
The association between HLA genes and radiological erosions in Malaysian patients with rheumatoid arthritis

Yeap SS, Mohd A, Kumar G, Kong KF, Chow SK, Goh EM, et al.

Autoimmunity, 2007 May;40(3):187-90.
PMID: 17453717 DOI: 10.1080/08916930701233755

OBJECTIVE:
To assess the relationship between the HLA-DRB1 genes with disease severity as assessed by radiological erosions in Malaysian patients with rheumatoid arthritis (RA).

METHODS:
In this cross-sectional study, we studied 61 RA patients who fulfilled the ACR criteria for the diagnosis of RA. HLA-DRB1 genotyping was performed by sequence specific primer (SSP) - PCR. Radiological grading and erosive score of the hands and wrists was calculated according to the Larsen-Dale method. Demographic data and treatment given to the patients were obtained from their case records.

RESULTS:
Fifty-six females and five males were studied from three ethnic groups. In 57 patients with erosions, rheumatoid factor was detected in 80%, HLA-DR4 in 40%, HLA-DRB1*0405 in 24% and shared epitope (SE) in 31%. The median delay in starting DMARDs was 24 months. The presence of rheumatoid factor, HLA-DR4 and HLA-DRB1*0405 were not significantly associated with a worse erosive score. Patients who possessed the SE had a higher erosive scores, compared to those who did not (p = 0.05). Concurrently, a delay in starting DMARD was associated with a high erosive score (p = 0.023, r = 0.348). However, after adjustment for the delay in starting DMARD, SE was no longer significantly associated with the erosive score.

CONCLUSIONS:
In these patients, the delay in starting DMARDs had a greater influence on the erosive score than SE alone. Whilst we cannot discount the contribution of the SE presence, we would advocate early usage of DMARDs in every RA patient to reduce joint erosions and future disability.
Metabolic syndrome and cardiometabolic risk factors among indigenous Malaysians

Aghakhanian F, Wong C, Tan JSY, Yeo LF, Ramadas A, Edo J, et al.

Public Health, 2019 Nov;176:106-113.
PMID: 30509859 DOI: 10.1016/j.puhe.2018.10.001

OBJECTIVES: This study was undertaken to investigate the occurrence of metabolic syndrome (MetS) and cardiovascular disease (CVD) risk in Orang Asli (OA), the indigenous people of Peninsular Malaysia. OA consist of Negrito, Proto-Malay, and Senoi groups who collectively comprise only 0.76% of the population of Peninsular Malaysia. Owing to the challenges in accessing their remote villages, these groups are often excluded in larger government health surveys. Although tropical diseases were scourges in the past, with rapid national development, many OA communities have been gradually urbanized. We believe an epidemiological transition is occurring and non-communicable diseases are on the rise.
STUDY DESIGN: A retrospective cross-sectional study.
METHODS: Indigenous Malaysians (n = 629) from three major groups (Negrito, Proto-Malay, and Senoi) were recruited, after ethics approval and informed consent. Body mass index (BMI), body weight, height, waist circumference, and systolic and diastolic blood pressure were measured, and participants were examined for acanthosis nigricans. Venous blood samples were used for measurements of fasting blood sugar, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Insulin resistance was estimated using a surrogate measurement TG/HDL-C. The ratios of TC to HDL-C, and of LDL-C to HDL-C were determined. MetS was accessed according to the Joint Interim Statement of the IDF Tsak Force on Epidemiology and Prevention.
RESULTS: MetS affected 29.57% of the OA population investigated and was significantly more prevalent (P