Displaying publications 101 - 120 of 301 in total

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  1. Kusuma P, Brucato N, Cox MP, Letellier T, Manan A, Nuraini C, et al.
    Eur J Hum Genet, 2017 08;25(8):1004-1010.
    PMID: 28513608 DOI: 10.1038/ejhg.2017.88
    The Bajo, the world's largest remaining sea nomad group, are scattered across hundreds of recently settled communities in Island Southeast Asia, along the coasts of Indonesia, Malaysia and the Philippines. With a significant role in historical trading, the Bajo lived until recently as nomads, spending their entire lives on houseboats while moving long distances to fish and trade. Along the routes they traveled, the Bajo settled and intermarried with local land-based groups, leading to 'maritime creolization', a process whereby Bajo communities retained their culture, but assimilated - and frequently married into - local groups. The origins of the Bajo have remained unclear despite several hypotheses from oral tradition, culture and language, all currently without supporting genetic evidence. Here, we report genome-wide SNP analyses on 73 Bajo individuals from three communities across Indonesia - the Derawan of Northeast Borneo, the Kotabaru of Southeast Borneo and the Kendari of Southeast Sulawesi, with 87 new samples from three populations surrounding the area where these Bajo peoples live. The Bajo likely share a common connection with Southern Sulawesi, but crucially, each Bajo community also exhibits unique genetic contributions from neighboring populations.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  2. Lee YC, Chan SH, Ren EC
    Immunogenetics, 2008 Nov;60(11):645-54.
    PMID: 18668235 DOI: 10.1007/s00251-008-0321-3
    Killer cell immunoglobulin-like receptors (KIR) gene frequencies have been shown to be distinctly different between populations and contribute to functional variation in the immune response. We have investigated KIR gene frequencies in 370 individuals representing three Asian populations in Singapore and report here the distribution of 14 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) with two pseudogenes (2DP1, 3DP1) among Singapore Chinese (n = 210); Singapore Malay (n = 80), and Singapore Indian (n = 80). Four framework genes (KIR3DL3, 3DP1, 2DL4, 3DL2) and a nonframework pseudogene 2DP1 were detected in all samples while KIR2DS2, 2DL2, 2DL5, and 2DS5 had the greatest significant variation across the three populations. Fifteen significant linkage patterns, consistent with associations between genes of A and B haplotypes, were observed. Eighty-four distinct KIR profiles were determined in our populations, 38 of which had not been described in other populations. KIR haplotype studies were performed using nine Singapore Chinese families comprising 34 individuals. All genotypes could be resolved into corresponding pairs of existing haplotypes with eight distinct KIR genotypes and eight different haplotypes. The haplotype A2 with frequency of 63.9% was dominant in Singapore Chinese, comparable to that reported in Korean and Chinese Han. The A haplotypes predominate in Singapore Chinese, with ratio of A to B haplotypes of approximately 3:1. Comparison with KIR frequencies in other populations showed that Singapore Chinese shared similar distributions with Chinese Han, Japanese, and Korean; Singapore Indian was found to be comparable with North Indian Hindus while Singapore Malay resembled the Thai.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  3. Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara K, Yamaguchi K, et al.
    Nat Genet, 2022 Nov;54(11):1640-1651.
    PMID: 36333501 DOI: 10.1038/s41588-022-01213-w
    Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  4. Liam CK, Leow HR, How SH, Pang YK, Chua KT, Lim BK, et al.
    Asian Pac J Cancer Prev, 2014;15(1):321-6.
    PMID: 24528049
    BACKGROUND: Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non- small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients.

    MATERIALS AND METHODS: In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction.

    RESULTS: EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94- 18.17; p=0.002).

    CONCLUSIONS: In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.

    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  5. Rehman A, Rasool AH, Naing L, Roshan TM, Rahman AR
    Ann. Hum. Genet., 2007 Jan;71(Pt 1):86-95.
    PMID: 17227479
    Angiotensin II type 1 receptor (AGT1R) gene 1166A > C polymorphism has been shown to be associated with essential hypertension and aortic stiffness as measured by carotid femoral pulse wave velocity (PWV). This study was carried out to investigate the association of the 1166A > C polymorphism with blood pressure (BP) and PWV among Malay hypertensive and normotensive subjects. Two hundred and one hypertensive subjects without evidence of cardiovascular (CV) complications and 201 age- and sex-matched normotensive subjects were studied in a cross-sectional design. Blood pressures (BP) and PWV were measured, and 1166A > C genotype was determined by polymerase chain reaction followed by restriction enzyme digestion. The 1166C allele frequency was 7.96% and 7.73% among Malay hypertensive and normotensive subjects, respectively. There was no association of the 1166A > C polymorphism with BP in the hypertensive, normotensive or overall Malay populations. PWV was significantly higher among 1166C allele carriers as compared to non-carriers (10.52 +/- 1.82 vs. 10.15 +/- 1.80, p = 0.040) in the overall population, but not in the hypertensive and normotensive populations separately. In conclusion, the frequency of 1166C polymorphism is similar among Malay hypertensive and normotensive subjects. This polymorphism has no association with BP but may have an influence on PWV in Malays, which needs further investigation.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  6. Teh LK, Ismail R, Yusoff R, Hussein A, Isa MN, Rahman AR
    J Clin Pharm Ther, 2001 Jun;26(3):205-11.
    PMID: 11422605
    Although Malays shared an origin with Chinese, their evolution saw substantial divergences. Phenotyping studies suggested that they differed in CYP2D6 polymorphism, with higher PM prevalence but lesser right-shift for debrisoquine MRs.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  7. Azizah MR, Ainoi SS, Kuak SH, Kong NCT, Normaznah Y, Rahim MN
    Asian Pac J Allergy Immunol, 2001 Jun;19(2):93-100.
    PMID: 11699726
    The frequency of the HLA class II antigens/alleles (HLA-DR, DQ and DP) were studied in 70 Malaysian Chinese patients with systemic lupus erythematosus (SLE) to examine the contribution of these genes to disease susceptibility, their clinical expression and Immunological responses. This was done using modified PCR-RFLP technique. These samples were then compared with 66 ethnically matched controls. We found a strong association of the DQA1*0102 (p corr = 0.032, rr = 3.39), DQB1*0501 (p corr = 0.003, rr = 4.55), *0601 (p corr = 0.006, rr = 4.22) and DPB1* 0901(p corr = 0.02, rr = 4.58) with SLE. Clinically, we found a strong association of DR2 and DQA1*0301 with renal involvement and DQA1*0102 with alopecia. Immunologically, statistical analysis (Chi-square test ) showed a strong association of DQA1*0102 with anti-Ro/La antibodies while DQA1*0301 was observed to be strongly associated with antibodies to ds DNA. DQA1*0102 was found more frequently in those with a later disease onset (30 years of age or above). From these data we suggest that the HLA class II genes play a role in conferring disease susceptibility and clinical and immunological expression.
    Study site: SLE clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  8. Azizah MR, Ainol SS, Kong NCT, Normaznah Y, Rahim MN
    Korean J. Intern. Med., 2001 Jun;16(2):123-31.
    PMID: 11590899 DOI: 10.3904/kjim.2001.16.2.123
    BACKGROUND: Studies have shown that certain genes within the major histocompatibility complex predispose to systemic lupus erythematosus (SLE) and may influence clinical and autoantibody expression. Thus, we studied the frequency of HLA-DR, -DQA, -DQB and -DPB alleles in ethnic Malays with SLE to determine the role of these genes in determining disease susceptibility and their association with clinical and immunological manifestations.
    METHODS: Fifty-six Malay SLE patients were enrolled into the study. Demographic, clinical and immunological findings were obtained from medical records. HLA-DR, DQ and DP typing were done using modified PCR-RELP. Controls were from ethnically-matched healthy individuals.
    RESULTS: We found a strongly significant association of the DR2 and DQB1 *0501 and DQB1*0601 (pcorr = 0.03, rr = 3.83, pcorr = 0.0036, rr = 4.56 and pcorr = 0.0048 and rr = 6.0, respectively). There was also a weak increase of DQB1*0.201 and DPB1*0.0901 with a weak decrease of DQA1*0601 and DQB1*0503 and *0301 which were not significant after corrections for multiple comparisons were made. There was a significant positive association of DR2 and DQB1*0501 with renal involvement and DR8 with alopecia. A nonsignificant increase of DQB1*0503 in patients with photosensitivity was noted. Significant autoantibody associations were also found: DQB1*0601 with anti-Sm/RNP, DR2 with antiSSA (Ro)/SSB (La), and DR2, DQB1*0501 and *0601 with antibodies to ds DNA. There was no specific DR, DQ or DP associations with age of disease onset (below 30 years or those at or above 30 years).
    CONCLUSION: Our data suggests the role of the HLA class II genes in conferring SLE susceptibility and in clinical and autoantibody expression.
    Study site: SLE Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  9. Liam CK, Pang YK, Poh ME
    J Thorac Oncol, 2014 Sep;9(9):e70-1.
    PMID: 25122441 DOI: 10.1097/JTO.0000000000000251
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  10. 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.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  11. Aghakhanian F, Yunus Y, Naidu R, Jinam T, Manica A, Hoh BP, et al.
    Genome Biol Evol, 2015 May;7(5):1206-15.
    PMID: 25877615 DOI: 10.1093/gbe/evv065
    Indigenous populations of Malaysia known as Orang Asli (OA) show huge morphological, anthropological, and linguistic diversity. However, the genetic history of these populations remained obscure. We performed a high-density array genotyping using over 2 million single nucleotide polymorphisms in three major groups of Negrito, Senoi, and Proto-Malay. Structural analyses indicated that although all OA groups are genetically closest to East Asian (EA) populations, they are substantially distinct. We identified a genetic affinity between Andamanese and Malaysian Negritos which may suggest an ancient link between these two groups. We also showed that Senoi and Proto-Malay may be admixtures between Negrito and EA populations. Formal admixture tests provided evidence of gene flow between Austro-Asiatic-speaking OAs and populations from Southeast Asia (SEA) and South China which suggest a widespread presence of these people in SEA before Austronesian expansion. Elevated linkage disequilibrium (LD) and enriched homozygosity found in OAs reflect isolation and bottlenecks experienced. Estimates based on Ne and LD indicated that these populations diverged from East Asians during the late Pleistocene (14.5 to 8 KYA). The continuum in divergence time from Negritos to Senoi and Proto-Malay in combination with ancestral markers provides evidences of multiple waves of migration into SEA starting with the first Out-of-Africa dispersals followed by Early Train and subsequent Austronesian expansions.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  12. Williams R, Periasamy M
    Endocrinol Metab (Seoul), 2020 12;35(4):681-695.
    PMID: 33397033 DOI: 10.3803/EnM.2020.772
    Obesity-associated metabolic illnesses are increasing at an alarming rate in Asian countries. A common feature observed in the Asian population is a higher incidence of abdominal obesity-the "skinny-fat" Asian syndrome. In this review, we critically evaluate the relative roles of genetics and environmental factors on fat distribution in Asian populations. While there is an upward trend in obesity among most Asian countries, it appears particularly conspicuous in Malaysia. We propose a novel theory, the Malaysian gene-environment multiplier hypothesis, which explains how ancestral variations in feast-and-famine cycles contribute to inherited genetic predispositions that, when acted on by modern-day stressors-most notably, urbanization, westernization, lifestyle changes, dietary transitions, cultural pressures, and stress-contribute to increased visceral adiposity in Asian populations. At present, the major determinants contributing to visceral adiposity in Asians are far from conclusive, but we seek to highlight critical areas for further research.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  13. Shia AK, Gan GG, Jairaman S, Peh SC
    J Clin Pathol, 2005 Sep;58(9):962-7.
    PMID: 16126878
    Recent reports have divided diffuse large B cell lymphoma (DLBCL) into germinal centre B cell-like and activated B cell-like subgroups with implicated differences in prognosis.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  14. 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.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  15. Wong F, Boo N, Othman A
    J Trop Pediatr, 2013 Aug;59(4):280-5.
    PMID: 23640907 DOI: 10.1093/tropej/fmt023
    To investigate the risk factors associated with neonatal hyperbilirubinemia in Malaysian neonates.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  16. Boo NY, Wong FL, Wang MK, Othman A
    Pediatr Int, 2009 Aug;51(4):488-93.
    PMID: 19674361 DOI: 10.1111/j.1442-200X.2008.02798.x
    The aim of the present study was to compare, in a case-control study, the prevalence of nucleotide 211 guanine to adenine (G-->A) mutation of uridine diphosphoglucuronosyl transferase (UGT1A1) gene in Malaysian Chinese newborns with and without severe hyperbilirubinemia (total serum bilirubin >250 micromol/L during first 48 h of life or > or =300 micromol/L thereafter), and to determine whether this mutation was a significant risk factor associated with severe hyperbilirubinemia.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  17. Tay CG, Ariffin H, Yap S, Rahmat K, Sthaneshwar P, Ong LC
    J Child Neurol, 2015 Jun;30(7):927-31.
    PMID: 25122112 DOI: 10.1177/0883073814540523
    Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessive disorder affecting catabolism of the neurotransmitter gamma-aminobutyric acid (GABA), with a wide range of clinical phenotype. We report a Malaysian Chinese boy with a severe early onset phenotype due to a previously unreported mutation. Urine organic acid chromatogram revealed elevated 4-hydroxybutyric acid. Magnetic resonance imaging (MRI) of the brain demonstrated cerebral atrophy with atypical putaminal involvement. Molecular genetic analysis showed a novel homozygous 3-bp deletion at the ALDH5A1 gene c.1501_1503del (p.Glu501del). Both parents were confirmed to be heterozygotes for the p.Glu501del mutation. The clinical course was complicated by the development of subdural hemorrhage probably as a result of rocking the child to sleep for erratic sleep-wake cycles. This case illustrates the need to recognize that trivial or unintentional shaking of such children, especially in the presence of cerebral atrophy, can lead to subdural hemorrhage.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
  18. Ho KH, Ong BK
    Headache, 2001 Mar;41(3):279-84.
    PMID: 11264688 DOI: 10.1046/j.1526-4610.2001.111006279.x
    This study presents the first account of the racial differences in headache prevalence and characteristics in the Singapore population. A questionnaire was administered to 2096 individuals from a randomized sample of 1400 households to test the hypothesis that race was independently correlated with headache diagnosis and morbidity. The overall lifetime prevalence of headaches in the study population was 82.7%; this did not vary between racial groups. The modal age of headache onset in all races was in the second decade and was similar in all races. Multivariate analysis showed that headache morbidity was independent of age, sex, income level, marital status, shift duties, and educational level, and correlated only with race and a positive family history of severe headache. Non-Chinese were more likely to suffer from severe headaches than Chinese, were more likely to seek medical attention, and were more likely to require medical leave for their symptoms. Non-Chinese had more migrainous headaches than Chinese, although characteristics of headache both groups experienced that were unrelated to severity differed only in a few aspects. We conclude that racial factors account for differences in headache classification, perception of headache severity and health-seeking behavior.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  19. Sakaue S, Hirata J, Kanai M, Suzuki K, Akiyama M, Lai Too C, et al.
    Nat Commun, 2020 03 26;11(1):1569.
    PMID: 32218440 DOI: 10.1038/s41467-020-15194-z
    The diversity in our genome is crucial to understanding the demographic history of worldwide populations. However, we have yet to know whether subtle genetic differences within a population can be disentangled, or whether they have an impact on complex traits. Here we apply dimensionality reduction methods (PCA, t-SNE, PCA-t-SNE, UMAP, and PCA-UMAP) to biobank-derived genomic data of a Japanese population (n = 169,719). Dimensionality reduction reveals fine-scale population structure, conspicuously differentiating adjacent insular subpopulations. We further enluciate the demographic landscape of these Japanese subpopulations using population genetics analyses. Finally, we perform phenome-wide polygenic risk score (PRS) analyses on 67 complex traits. Differences in PRS between the deconvoluted subpopulations are not always concordant with those in the observed phenotypes, suggesting that the PRS differences might reflect biases from the uncorrected structure, in a trait-dependent manner. This study suggests that such an uncorrected structure can be a potential pitfall in the clinical application of PRS.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics*
  20. Azira NM, Zeehaida M, Nurul Khaiza Y
    Malays J Pathol, 2013 Jun;35(1):65-9.
    PMID: 23817396 MyJurnal
    The human leucocyte antigen (HLA) has been documented to be involved in various disease susceptibilities or in resistance against certain diseases. An important element in susceptibility and resistance to disease is ethnic genetic constitution. Cognizant of this, the present study aimed at studying the prevalence of particular HLA class II in a normal healthy Malay population which may serve as a guide for further genetic and immunological studies related to the Malay Malaysian population. The study involved 40 normal healthy Malay persons in Kelantan. HLA typing was conducted on venous blood samples through a polymerase chain reaction-sequence specific primer method (low resolution Olerup SSP© HLA Typing Kits). The study found HLA DR12 and HLA DQ8 to be the most frequent HLA class II type. HLA DQ5 was significantly associated with female subjects.
    Matched MeSH terms: Asian Continental Ancestry Group/genetics
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