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  1. Further observations in an area with an exceptionally low prevalence of Helicobacter pylori infection
    Raj SM, Lee YY, Choo KE, Noorizan AM, Zulkifli A, Radzi M, et al.
    Trans R Soc Trop Med Hyg, 2008 Nov;102(11):1163-4.
    PMID: 18678380 DOI: 10.1016/j.trstmh.2008.06.015
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  2. Clinical implications of single- versus multiple-site keloid disorder: a retrospective study in an Asian population
    Park TH, Park JH, Tirgan MH, Halim AS, Chang CH
    Ann Plast Surg, 2015 Feb;74(2):248-51.
    PMID: 24681623 DOI: 10.1097/SAP.0b013e3182a2b537
    There is strong evidence of genetic susceptibility in individuals with keloid disorder. The purpose of this cross-sectional study was to determine the clinical relevance of our proposed variables on the multiplicity of keloids by further investigating the presence of other keloids and a family history.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology*
  3. Toward cultural competence in cancer genetic counseling and genetics education: lessons learned from Chinese-Australians
    Barlow-Stewart K, Yeo SS, Meiser B, Goldstein D, Tucker K, Eisenbruch M
    Genet Med, 2006 Jan;8(1):24-32.
    PMID: 16418596
    PURPOSE: In societies such as Australia with a strong multicultural makeup, culturally determined attitudes to genetics, testing, and counseling may be incompatible with current genetics service provision.

    METHODS: An ethnographic investigation using purposive sampling to increase subject diversity was used to explore the range of beliefs about kinship and inheritance using Chinese-Australians as a case. Participants comprised a sample of 15 Chinese-Australians who had been recruited through several community-based organizations.

    RESULTS: The level of acculturation does not correlate with holding beliefs about inheritance, kinship, and causes of hereditary cancer that are based on "Western" biomedical or traditional concepts. Mismatch between beliefs may exist within families that can impact participation in cancer genetic testing. Family history taking that underpins the surveillance, management, and referral to genetic counseling where there is a strong family history of breast, ovarian, or colorectal cancer can also be impacted unless recognition is made of the patrilineal concept of kinship prevalent in this Chinese-Australian community.

    CONCLUSION: This community-based study confirmed and validated views and beliefs on inheritance and kinship and inherited cancer attributed to senior family members by Chinese-Australians who attended cancer genetic counseling. Barriers to communication can occur where there may be incompatibility within the family between "Western" and traditional beliefs. The findings were used to develop strategies for culturally competent cancer genetic counseling with Australian-Chinese patients. These include nonjudgmental incorporation of their belief systems into the genetic counseling process and avoidance of stereotyping. They have also influenced the development of genetics education materials to optimize family history taking.

    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  4. Copy number polymorphisms in new HapMap III and Singapore populations
    Ku CS, Teo SM, Naidoo N, Sim X, Teo YY, Pawitan Y, et al.
    J Hum Genet, 2011 Aug;56(8):552-60.
    PMID: 21677662 DOI: 10.1038/jhg.2011.54
    Copy number variations can be identified using newer genotyping arrays with higher single nucleotide polymorphisms (SNPs) density and copy number probes accompanied by newer algorithms. McCarroll et al. (2008) applied these to the HapMap II samples and identified 1316 copy number polymorphisms (CNPs). In our study, we applied the same approach to 859 samples from three Singapore populations and seven HapMap III populations. Approximately 50% of the 1291 autosomal CNPs were found to be polymorphic only in populations of non-African ancestry. Pairwise comparisons among the 10 populations showed substantial differences in the CNPs frequencies. Additionally, 698 CNPs showed significant differences with false discovery rate (FDR)<0.01 among the 10 populations and these loci overlap with known disease-associated or pharmacogenetic-related genes such as CFHR3 and CFHR1 (age related macular degeneration), GSTTI (metabolism of various carcinogenic compounds and cancers) and UGT2B17 (prostate cancer and graft-versus-host disease). The correlations between CNPs and genome-wide association studies-SNPs were investigated and several loci, which were previously unreported, that may potentially be implicated in complex diseases and traits were found; for example, childhood acute lymphoblastic leukaemia, age-related macular degeneration, breast cancer, response to antipsychotic treatment, rheumatoid arthritis and type-1 diabetes. Additionally, we also found 5014 novel copy number loci that have not been reported previously by McCarroll et al. (2008) in the 10 populations.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  5. Identification of DLG5 and SLC22A5 gene polymorphisms in Malaysian patients with Crohn's disease
    Chua KH, Lian LH, Kee BP, Thum CM, Lee WS, Hilmi I, et al.
    J Dig Dis, 2011 Dec;12(6):459-66.
    PMID: 22118696 DOI: 10.1111/j.1751-2980.2011.00533.x
    The aim of this study was to investigate the association of DLG5 and SLC22A5 gene polymorphisms with the onset of Crohn's disease (CD) in a Malaysian cohort.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  6. Lack of association between synapsin II (SYN2) gene polymorphism and susceptibility epilepsy: a case-control study and meta-analysis
    Haerian BS, Lim KS, Tan HJ, Wong CP, Wong SW, Tan CT, et al.
    Synapse, 2011 Oct;65(10):1073-9.
    PMID: 21465568 DOI: 10.1002/syn.20939
    The SYN2 rs3773364 A>G polymorphism has been proposed to be involved in susceptibility to epilepsy, but research results have been inconclusive. The aim of this study was to investigate the association between the SYN2 rs3773364 A>G polymorphism and susceptibility against epilepsy in a case-control study and a meta-analysis.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  7. Genomic copy number variations in three Southeast Asian populations
    Ku CS, Pawitan Y, Sim X, Ong RT, Seielstad M, Lee EJ, et al.
    Hum Mutat, 2010 Jul;31(7):851-7.
    PMID: 20506136 DOI: 10.1002/humu.21287
    Research on the role of copy number variations (CNVs) in the genetic risk of diseases in Asian populations has been hampered by a relative lack of reference CNV maps for Asian populations outside the East Asians. In this article, we report the population characteristics of CNVs in Chinese, Malay, and Asian Indian populations in Singapore. Using the Illumina Human 1M Beadchip array, we identify 1,174 CNV loci in these populations that corroborated with findings when the same samples were typed on the Affymetrix 6.0 platform. We identify 441 novel loci not previously reported in the Database of Genomic Variations (DGV). We observe a considerable number of loci that span all three populations and were previously unreported, as well as population-specific loci that are quite common in the respective populations. From this we observe the distribution of CNVs in the Asian Indian population to be considerably different from the Chinese and Malay populations. About half of the deletion loci and three-quarters of duplication loci overlap UCSC genes. Tens of loci show population differentiation and overlap with genes previously known to be associated with genetic risk of diseases. One of these loci is the CYP2A6 deletion, previously linked to reduced susceptibility to lung cancer.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  8. Distribution of PON1 polymorphisms PON1Q192R and PON1L55M among Chinese, Malay and Indian males in Singapore and possible susceptibility to organophosphate exposure
    Chia SE, Mohamed Ali S, Yap PH, Gan L, Ong YB, Chia KS
    Neurotoxicology, 2009 Mar;30(2):214-9.
    PMID: 19135476 DOI: 10.1016/j.neuro.2008.12.004
    Organophosphate (OP)-containing pesticides are widely used worldwide for domestic and industrial purposes. Studies on acute and chronic exposure to OPs have revealed numerous health effects attributed mainly to acetylcholinesterase (AChE) inhibition. The enzyme human serum paraoxonase (PON1) is involved in the detoxification of OP compounds. PON1 polymorphisms have been shown to affect susceptibility to OP exposure. We studied the effect of OP exposure on pest control workers and assessed the distribution of two common PON1 polymorphisms in our local population. The exposed group consisted of 103 workers from various pest control companies under the Singapore Pest Management Association while the 91 unexposed workers were from a lead stabilizer factory. For all workers, the mean age was 36.9 (20-70) years and the ethnic distribution was 38.1% Chinese, 44.3% Malay and 17.5% Indian. The mean+/-S.D. exposure duration among the pesticide workers was 10.4+/-8.4 years. The mean+/-S.D. RBC cholinesterase level was 18436.2+/-2078U/L and 18079.6+/-1576U/L for the exposed and unexposed groups, respectively (p=0.216). The mean+/-S.D. serum pseudocholinesterase was 11028.4+/-2867.4U/L and 9433.6+/-2022.6U/L in the exposed and unexposed groups, respectively (p<0.0001). Mean paraoxonase activity was similar among Chinese and Malays (266.5 and 266.3U/L, respectively) whereas that of the Indians was significantly lower (165.6U/L). Our study showed that cholinesterase levels among the exposed were not lower than those in the unexposed group. PON1 polymorphisms differed among ethnic groups, implying that ethnicity could be an important surrogate for identifying susceptible groups in case of OP exposure. Although OP poisoning is rare among occupationally exposed workers in Singapore, this information is useful for other developing countries that have large populations of Chinese, Malays and Indians where OP exposure could be very high especially in agricultural settings.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  9. Fulltext Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer
    Milne RL, Kuchenbaecker KB, Michailidou K, Beesley J, Kar S, Lindström S, et al.
    Nat Genet, 2017 Dec;49(12):1767-1778.
    PMID: 29058716 DOI: 10.1038/ng.3785
    Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  10. Fulltext Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis in diverse Asian populations: evidence from MyEIRA study and meta-analysis
    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: Genetic Predisposition to Disease/ethnology
  11. TNFSF4 polymorphisms are associated with systemic lupus erythematosus in the Malaysian population
    Chua KH, Ooh YY, Chai HC
    Int. J. Immunogenet., 2016 Oct;43(5):303-9.
    PMID: 27519474 DOI: 10.1111/iji.12287
    Tumour necrosis factor superfamily 4 (TNFSF4) gene has been reported to be associated with systemic lupus erythematosus (SLE) susceptibility due to its encoding for OX40L protein that can increase autoantibody production and cause imbalance of T-cell proliferation. The purpose of this study was to investigate the association of TNFSF4 rs2205960, rs1234315, rs8446748 and rs704840 with SLE in the Malaysian population. A total of 476 patients with SLE and 509 healthy controls were recruited. Real-time polymerase chain reaction (PCR) was applied to genotype the selected single nucleotide polymorphisms (SNPs). Allelic and genotypic frequencies of each SNP were calculated for each ethnic group, and association test was performed using logistic regression. The overall association of each SNP in Malaysian patients with SLE was determined with meta-analysis. The frequency of minor T allele of TNFSF4 rs2205960 was significant in Chinese and Indian patients with SLE, with P values of 0.05 (OR = 1.27, 95% CI: 1.00-1.61) and 0.004 (OR = 3.16, 95% CI: 1.41-7.05), respectively. Significant association of minor G allele of rs704840 with SLE was also observed in Chinese (P = 0.03, OR = 1.26, 95% CI: 1.02-1.56). However, after Bonferroni correction, only T allele of rs2205960 remained significantly associated with Indian cohort. Overall, minor G allele of rs704840 showed significant association with SLE in the Malaysian population with P values of 0.05 (OR = 1.20, 95% CI: 1.00-1.43). We suggested TNFSF4 rs704840 could be the potential SLE risk factors in the Malaysian population.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  12. Fulltext Association and interaction between dietary pattern and VEGF receptor-2 (VEGFR2) gene polymorphisms on blood lipids in Chinese Malaysian and Japanese adults
    Yap RW, Shidoji Y, Hon WM, Masaki M
    Asia Pac J Clin Nutr, 2012;21(2):302-11.
    PMID: 22507619
    Dietary pattern and genetic predisposition of each population have different impacts on lifestyle-related chronic diseases. This study was conducted to evaluate the association and interaction between dietary patterns and VEGFR2 or KDR gene polymorphisms on physical and biochemical risk factors of cardiovascular disease in two Asian populations (179 Chinese Malaysian and 136 Japanese adults).
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  13. Haplotype diversity in 11 candidate genes across four populations
    Beaty TH, Fallin MD, Hetmanski JB, McIntosh I, Chong SS, Ingersoll R, et al.
    Genetics, 2005 Sep;171(1):259-67.
    PMID: 15965248
    Analysis of haplotypes based on multiple single-nucleotide polymorphisms (SNP) is becoming common for both candidate gene and fine-mapping studies. Before embarking on studies of haplotypes from genetically distinct populations, however, it is important to consider variation both in linkage disequilibrium (LD) and in haplotype frequencies within and across populations, as both vary. Such diversity will influence the choice of "tagging" SNPs for candidate gene or whole-genome association studies because some markers will not be polymorphic in all samples and some haplotypes will be poorly represented or completely absent. Here we analyze 11 genes, originally chosen as candidate genes for oral clefts, where multiple markers were genotyped on individuals from four populations. Estimated haplotype frequencies, measures of pairwise LD, and genetic diversity were computed for 135 European-Americans, 57 Chinese-Singaporeans, 45 Malay-Singaporeans, and 46 Indian-Singaporeans. Patterns of pairwise LD were compared across these four populations and haplotype frequencies were used to assess genetic variation. Although these populations are fairly similar in allele frequencies and overall patterns of LD, both haplotype frequencies and genetic diversity varied significantly across populations. Such haplotype diversity has implications for designing studies of association involving samples from genetically distinct populations.
    Matched MeSH terms: Genetic Predisposition to Disease/ethnology*
  14. Fulltext A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci
    Low JS, Chin YM, Mushiroda T, Kubo M, Govindasamy GK, Pua KC, et al.
    PLoS One, 2016;11(1):e0145774.
    PMID: 26730743 DOI: 10.1371/journal.pone.0145774
    BACKGROUND: Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition.

    METHODS: A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124).

    RESULTS: Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes.

    CONCLUSION: Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

    Matched MeSH terms: Genetic Predisposition to Disease/ethnology
  15. Fulltext The association of the HLA class II antigens with clinical and autoantibody expression in Malaysian Chinese patients with systemic lupus erythematosus
    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: Genetic Predisposition to Disease/ethnology
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