Displaying publications 41 - 60 of 72 in total

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  1. Fulltext Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1
    Cai Q, Zhang B, Sung H, Low SK, Kweon SS, Lu W, et al.
    Nat Genet, 2014 Aug;46(8):886-90.
    PMID: 25038754 DOI: 10.1038/ng.3041
    In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P=8.82×10(-9)), rs10474352 at 5q14.3 (near the ARRDC3 gene; P=1.67×10(-9)) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P=4.25×10(-8)). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P=0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  2. Fulltext 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy
    Li J, Lindström LS, Foo JN, Rafiq S, Schmidt MK, Pharoah PD, et al.
    Nat Commun, 2014 Jun 17;5:4051.
    PMID: 24937182 DOI: 10.1038/ncomms5051
    Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  3. Neuregulin-1 (NRG-1) and its susceptibility to schizophrenia: a case-control study and meta-analysis
    Loh HC, Tang PY, Tee SF, Chow TJ, Choong CY, Lim SY, et al.
    Psychiatry Res, 2013 Jul 30;208(2):186-8.
    PMID: 23489597 DOI: 10.1016/j.psychres.2013.01.022
    Neuregulin-1 is widely investigated due to its hypothesised association with schizophrenia. Single-nucleotide polymorphisms rs764059, rs2954041 and rs3924999 were investigated (417 patients with schizophrenia and 429 controls). We failed to demonstrate a significant association between rs2954041 and rs3924999 with schizophrenia in the three ethnic groups studied (Malay, Chinese, and Indian), while rs764059 was found to be monomorphic.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  4. Fulltext The impact of SLCO1B1 genetic polymorphisms on neonatal hyperbilirubinemia: a systematic review with meta-analysis
    Liu J, Long J, Zhang S, Fang X, Luo Y
    J Pediatr (Rio J), 2013 07 11;89(5):434-43.
    PMID: 23850112 DOI: 10.1016/j.jped.2013.01.008
    OBJECTIVE: To determine whether three variants (388 G>A, 521 T>C, and 463 C>A) of the solute carrier organic anion transporter family member 1B1 (SLCO1B1) are associated with neonatal hyperbilirubinemia.

    DATA SOURCE: The China National Knowledge Infrastructure and MEDLINE databases were searched. The systematic review with meta-analysis included genetic studies which assessed the association between neonatal hyperbilirubinemia and 388 G>A, 521 T>C, and 463 C>A variants of SLCO1B1 between January of 1980 and December of 2012. Data selection and extraction were performed independently by two reviewers.

    SUMMARY OF THE FINDINGS: Ten articles were included in the study. The results revealed that SLCO1B1 388 G>A is associated with an increased risk of neonatal hyperbilirubinemia (OR, 1.39; 95% CI, 1.07-1.82) in Chinese neonates, but not in white, Thai, Latin American, or Malaysian neonates. The SLCO1B1 521 T>C mutation showed a low risk of neonatal hyperbilirubinemia in Chinese neonates, while no significant associations were found in Brazilian, white, Asian, Thai, and Malaysian neonates. There were no significant differences in SLCO1B1 463 C>A between the hyperbilirubinemia and the control group.

    CONCLUSION: This study demonstrated that the 388 G>A mutation of the SLCO1B1 gene is a risk factor for developing neonatal hyperbilirubinemia in Chinese neonates, but not in white, Thai, Brazilian, or Malaysian populations; the SLCO1B1 521 T>C mutation provides protection for neonatal hyperbilirubinemia in Chinese neonates, but not in white, Thai, Brazilian, or Malaysian populations.

    Matched MeSH terms: European Continental Ancestry Group/genetics
  5. Fulltext Genetic polymorphisms of human platelet antigens-1 to -6, and -15 in the Malaysian population
    Tan JY, Lian LH, Nadarajan VS
    Blood Transfus, 2012 Jul;10(3):368-76.
    PMID: 22682339 DOI: 10.2450/2012.0095-11
    Human platelet antigens (HPA) are determinant in several platelet-specific alloimmune disorders, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura and platelet transfusion refractoriness. The distribution of HPA systems in the Malaysian population is not known. Defining the patterns of HPA systems provides a basis for risk assessment and management of the above complications.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  6. CYP2C19 and PON1 polymorphisms regulating clopidogrel bioactivation in Chinese, Malay and Indian subjects
    Chan MY, Tan K, Tan HC, Huan PT, Li B, Phua QH, et al.
    Pharmacogenomics, 2012 Apr;13(5):533-42.
    PMID: 22462746 DOI: 10.2217/pgs.12.24
    AIM, MATERIALS & METHODS: We investigated the functional significance of CYP2C19*2, *3, *17 and PON1 Q192R SNPs in 89 consecutive Asian patients on clopidogrel treatment and the prevalence of functionally significant polymorphisms among 300 Chinese, Malays and Asian Indians.
    Matched MeSH terms: European Continental Ancestry Group/genetics*
  7. Replication of 13 obesity loci among Singaporean Chinese, Malay and Asian-Indian populations
    Dorajoo R, Blakemore AI, Sim X, Ong RT, Ng DP, Seielstad M, et al.
    Int J Obes (Lond), 2012 Jan;36(1):159-63.
    PMID: 21544081 DOI: 10.1038/ijo.2011.86
    Recent genome-wide association studies (GWAS) have identified 38 obesity-associated loci among European populations. However, their contribution to obesity in other ethnicities is largely unknown.
    Matched MeSH terms: European Continental Ancestry Group/genetics*
  8. Fulltext Skin color variation in Orang Asli tribes of Peninsular Malaysia
    Ang KC, Ngu MS, Reid KP, Teh MS, Aida ZS, Koh DX, et al.
    PLoS One, 2012;7(8):e42752.
    PMID: 22912732 DOI: 10.1371/journal.pone.0042752
    Pigmentation is a readily scorable and quantitative human phenotype, making it an excellent model for studying multifactorial traits and diseases. Convergent human evolution from the ancestral state, darker skin, towards lighter skin colors involved divergent genetic mechanisms in people of European vs. East Asian ancestry. It is striking that the European mechanisms result in a 10-20-fold increase in skin cancer susceptibility while the East Asian mechanisms do not. Towards the mapping of genes that contribute to East Asian pigmentation there is need for one or more populations that are admixed for ancestral and East Asian ancestry, but with minimal European contribution. This requirement is fulfilled by the Senoi, one of three indigenous tribes of Peninsular Malaysia collectively known as the Orang Asli. The Senoi are thought to be an admixture of the Negrito, an ancestral dark-skinned population representing the second of three Orang Asli tribes, and regional Mongoloid populations of Indo-China such as the Proto-Malay, the third Orang Asli tribe. We have calculated skin reflectance-based melanin indices in 492 Orang Asli, which ranged from 28 (lightest) to 75 (darkest); both extremes were represented in the Senoi. Population averages were 56 for Negrito, 42 for Proto-Malay, and 46 for Senoi. The derived allele frequencies for SLC24A5 and SLC45A2 in the Senoi were 0.04 and 0.02, respectively, consistent with greater South Asian than European admixture. Females and individuals with the A111T mutation had significantly lighter skin (p = 0.001 and 0.0039, respectively). Individuals with these derived alleles were found across the spectrum of skin color, indicating an overriding effect of strong skin lightening alleles of East Asian origin. These results suggest that the Senoi are suitable for mapping East Asian skin color genes.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  9. 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: European Continental Ancestry Group/genetics
  10. Fulltext Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy
    Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.
    Seizure, 2011 Jun;20(5):387-94.
    PMID: 21316268 DOI: 10.1016/j.seizure.2011.01.008
    It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy.
    Matched MeSH terms: European Continental Ancestry Group/genetics*
  11. Interethnic comparisons of important pharmacology genes using SNP databases: potential application to drug regulatory assessments
    Chen J, Teo YY, Toh DS, Sung C
    Pharmacogenomics, 2010 Aug;11(8):1077-94.
    PMID: 20712526 DOI: 10.2217/pgs.10.79
    The frequencies of alleles implicated in drug-response variability provide vital information for public health management. Differences in frequencies between genetically diverse groups of individuals can hamper drug assessments, particularly in populations where clinical data are not readily available.
    Matched MeSH terms: European Continental Ancestry Group/genetics*
  12. Pharmacogenetics of CYP1A2, novel polymorphisms and haplotypes in three distinct Asian populations
    Lim JS, Singh O, Ramasamy RD, Ramasamy S, Subramanian K, Lee EJ, et al.
    Drug Metab. Pharmacokinet., 2010;25(6):616-23.
    PMID: 20930417
    CYP1A2 play an important role in the metabolism of many carcinogens and clinically important drugs. CYP1A2 activity has been found to be influenced by the presence of polymorphic variants which were reported to display wide interethnic variation. This study investigates the frequency distribution and linkage disequilibrium patterns of CYP1A2 genetic polymorphisms, and characterize their haplotype structures in three healthy Asian populations in Singapore (Chinese, Malay, and Indian). The entire CYP1A2 gene was screened in 126 healthy subjects from all three ethnic groups (N=42 each). A total of 25 polymorphisms was identified, of which nine were novel. The polymorphisms, -2467delT and -163C>A were detected at high frequencies in all Asian ethnic groups. Significant interethnic differences were observed in the genotypic frequency distribution of IVS2-99G>A (P<0.01) and 1548C>T (P=0.05) across the three ethnic groups while -163C>A (P=0.02) was found to differ between Chinese and Malays. Haplotype analyses revealed four to six major haplotypes in each ethnic population which accounted for more than 60% of the cumulative haplotype frequencies. Future studies should be done to investigate the functional roles of these haplotypes.
    Matched MeSH terms: European Continental Ancestry Group/genetics*
  13. Single step PCR for detection of allelic variation of MDR1 gene (P-glycoprotein) among three ethnic groups in Malaysia
    Teh LK, Lee WL, Amir J, Salleh MZ, Ismail R
    J Clin Pharm Ther, 2007 Jun;32(3):313-9.
    PMID: 17489883
    P-glycoprotein (PgP) is the most extensively studied ATP-binding cassette (ABC) coded by MDR1 gene. To date, 29 single nucleotide polymorphisms (SNPs) have been identified; but only SNP C3435T has been correlated with intestinal PgP expression levels and shown to influence the absorption of orally taken drugs that are PgP substrates. Individuals homozygous for the T allele have more than fourfold lower PgP expression compared with C/C individuals. We developed a one step primer based allele specific PCR method to detect SNP at C3435T to investigate the distribution of this genotype in the local population.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  14. A distinct Y-STR haplotype for Amelogenin negative males characterized by a large Y(p)11.2 (DYS458-MSY1-AMEL-Y) deletion
    Chang YM, Perumal R, Keat PY, Yong RY, Kuehn DL, Burgoyne L
    Forensic Sci Int, 2007 Mar 2;166(2-3):115-20.
    PMID: 16765004
    The use of STR multiplexes with the incorporated gender marker Amelogenin is common practice in forensic DNA analysis. However, when a known male sample shows a dropout of the Amelogenin Y-allele, the STR system falsely genotypes it as a female. To date, our laboratory has observed 18 such cases: 12 from our Y-STR database and six from casework. A study on 980 male individuals in the Malaysian population using the AmpFlSTR Y-filer has revealed a distinct Y-chromosome haplotype associated with the Amelogenin nulls. Our results showed that whilst the Amelogenin nulls were noticeably absent among the Chinese, both the Indians and Malays exhibited such mutations at 3.2 and 0.6%, respectively. It was also found that the Amelogenin negative individuals predominantly belonged to the J2e lineage, suggesting the possibility of a common ancestor for at least some of these chromosomes. The null frequencies showed concordance with the data published in Chang et al. [Higher failures of Amelogenin sex test in an Indian population group, J. Forensic Sci. 48 (2003) 1309-1313] on a smaller Malaysian population of 338 males which used a Y-STR triplex. In the current study, apart from the absence of the Amelogenin Y-locus, a complete absence of the DYS458 locus in all the nulls was also observed. This study together with the 2003 study has indicated a similar deletion region exists on the Y(p)11.2 band in all the 18 Y-chromosomes. Using bioinformatics, this deletion has been mapped to a region of at least 1.13 Mb on the Y(p)11.2 encompassing the Amelogenin, MSY1 minisatellite and DYS458 locus. Further, the Y-filer haplotypes revealed an additional null at Y-GATA H4 in two of the Indian males presented here.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  15. The promoter region of the MDR1 gene is largely invariant, but different single nucleotide polymorphism haplotypes affect MDR1 promoter activity differently in different cell lines
    Wang B, Ngoi S, Wang J, Chong SS, Lee CG
    Mol. Pharmacol., 2006 Jul;70(1):267-76.
    PMID: 16608921
    The MDR1 multidrug transporter represents one of the better characterized drug transporters that play an important role in protecting the body against xenobiotic insults. Single nucleotide polymorphisms (SNPs) and SNP haplotypes within this gene have been variously associated with differences in MDR1 expression/function, drug response as well as disease susceptibility. Nonetheless, the effect of polymorphisms at the MDR1 promoter region on its promoter activity remains less characterized. Through the examination of approximately 1.5 kilobases of MDR1 promoter region from five populations, including the Chinese, Malays, Indians, European Americans, and African Americans, we identified eight low-frequency SNPs, of which only two were polymorphic in at least four of the five populations examined. The other SNPs are mainly population-specific, the majority of which occur only in the African-American population. Recapitulation of the various combinations of SNP haplotypes in vitro in promoter-reporter assays revealed a few notable trends. The African and European American-specific haplotypes tended to result in enhanced MDR1 promoter activity only in the human embryonic kidney (HEK) 293 cell line. Haplotype GCTAACC, which occurs at variable frequencies in all the populations examined, with Asians having much lower frequencies (<2%) compared with the European Americans/African Americans (>4%), affected MDR1 promoter activity differently in different cell lines. Compared with the commonest haplotype, GCTA-ACC haplotype resulted in a significant decrease in MDR1 promoter activity in HeLa cells (P < 0.05) but a significant increase in the same promoter activity in HEK293 cells (P < 0.05). These results suggest that the MDR1 promoter region is largely invariant but that different haplotypes have differential effects on the MDR1 promoter activity in different cell lines.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  16. Malaysian Indians are genetically similar to Caucasians: CYP2C9 polymorphism
    Zainuddin Z, Teh LK, Suhaimi AW, Ismail R
    J Clin Pharm Ther, 2006 Apr;31(2):187-91.
    PMID: 16635054
    CYP2C9 is one of the major drug metabolizing enzymes for many drugs including warfarin, NSAIDs and losartan. It is polymorphic in many populations. Data on the distribution of CYP2C9 and the implication of CYP2C9 polymorphism in the Malaysian population is lacking. Our objectives were therefore to investigate the prevalence of CYP2C9 variants among unrelated healthy volunteers of Malays, Chinese and Indians in Malaysia.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  17. CYP2D6 genotype and phenotype relationship in South Indians
    Ismail R
    J Postgrad Med, 2006 Oct-Dec;52(4):245.
    PMID: 17243206
    Matched MeSH terms: European Continental Ancestry Group/genetics*
  18. 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: European Continental Ancestry Group/genetics*
  19. ABCA1 gene polymorphisms and their associations with coronary artery disease and plasma lipids in males from three ethnic populations in Singapore
    Tan JH, Low PS, Tan YS, Tong MC, Saha N, Yang H, et al.
    Hum Genet, 2003 Jul;113(2):106-17.
    PMID: 12709788
    Mutations in the ATP-binding cassette transporter ABCA1 underlie Tangier disease and familial hypoalphaliproteinemia (FHA), disorders that are characterised by reduced high-density lipoprotein-cholesterol (HDL-C) concentration and cholesterol efflux, and increased coronary artery disease (CAD). We explored if polymorphisms in the ABCA1 gene are associated with CAD and variations in plasma lipid levels, especially HDL-C, and whether the associations may depend on ethnicity. Male cases and controls from the Singapore Chinese, Malay and Indian populations were genotyped for five ABCA1 single nucleotide polymorphisms. Various single-locus frequency distribution differences between cases and controls were detected in different ethnic groups: the promoter -14C>T in Indians, exon 18 M883I in Malays, and 3'-untranslated (UTR) region 8994A>G in Chinese. For the Malay population, certain haplotypes carrying the I825- A (exon 17) and M883- G alleles were more frequent among cases than controls, whereas the converse was true for the alternative configuration of V825- G and I883- A, and this association was reinforced in multi-locus disequilibrium analysis that utilized genotypic data. In the healthy controls, associations were found for -14C>T genotypes with HDL-C in Chinese; 237indelG (5'UTR) with apolipoprotein A1 (apoA1) in Malays and total cholesterol (TC) in Indians; M883I with lipoprotein(a) [Lp(a)] in Malays and apolipoprotein B (apoB) in Chinese; and 8994A>G with Lp(a) in Malays, and TC, low-density lipoprotein-cholesterol (LDL-C) as well as apoB in Indians. While genotype-phenotype associations were not reproduced across populations and loci, V825I and M883I were clearly associated with CAD status in Malays with no effects on HDL-C or apoA1.
    Matched MeSH terms: European Continental Ancestry Group/genetics*
  20. Genetic polymorphism of CYP2D6: Malaysian Indians have the highest frequency for CYP2D6*4 in Asia
    Ismail R, Teh LK
    Eur J Clin Pharmacol, 2001 Oct;57(8):617-8.
    PMID: 11758642
    Matched MeSH terms: European Continental Ancestry Group/genetics*
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