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  1. Fulltext Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression
    Darabi H, McCue K, Beesley J, Michailidou K, Nord S, Kar S, et al.
    Am J Hum Genet, 2015 Jul 02;97(1):22-34.
    PMID: 26073781 DOI: 10.1016/j.ajhg.2015.05.002
    Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  2. Fulltext Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry
    Darst BF, Shen J, Madduri RK, Rodriguez AA, Xiao Y, Sheng X, et al.
    Am J Hum Genet, 2023 Jul 06;110(7):1200-1206.
    PMID: 37311464 DOI: 10.1016/j.ajhg.2023.05.010
    Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  3. Fulltext Noonan syndrome in diverse populations
    Kruszka P, Porras AR, Addissie YA, Moresco A, Medrano S, Mok GTK, et al.
    Am J Med Genet A, 2017 Sep;173(9):2323-2334.
    PMID: 28748642 DOI: 10.1002/ajmg.a.38362
    Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  4. Fulltext Turner syndrome in diverse populations
    Kruszka P, Addissie YA, Tekendo-Ngongang C, Jones KL, Savage SK, Gupta N, et al.
    Am J Med Genet A, 2020 Feb;182(2):303-313.
    PMID: 31854143 DOI: 10.1002/ajmg.a.61461
    Turner syndrome (TS) is a common multiple congenital anomaly syndrome resulting from complete or partial absence of the second X chromosome. In this study, we explore the phenotype of TS in diverse populations using clinical examination and facial analysis technology. Clinical data from 78 individuals and images from 108 individuals with TS from 19 different countries were analyzed. Individuals were grouped into categories of African descent (African), Asian, Latin American, Caucasian (European descent), and Middle Eastern. The most common phenotype features across all population groups were short stature (86%), cubitus valgus (76%), and low posterior hairline 70%. Two facial analysis technology experiments were conducted: TS versus general population and TS versus Noonan syndrome. Across all ethnicities, facial analysis was accurate in diagnosing TS from frontal facial images as measured by the area under the curve (AUC). An AUC of 0.903 (p < .001) was found for TS versus general population controls and 0.925 (p < .001) for TS versus individuals with Noonan syndrome. In summary, we present consistent clinical findings from global populations with TS and additionally demonstrate that facial analysis technology can accurately distinguish TS from the general population and Noonan syndrome.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  5. Activated protein C resistance: a study among 60 thromboembolic patients in the Singapore population
    Lim LC, Tan HH, Lee LH, Tien SL, Abdul Ghafar A
    Ann Acad Med Singap, 1999 Mar;28(2):252-5.
    PMID: 10497677
    Resistance to activated protein C (APC-R) is the commonest inherited cause of thrombosis among Caucasians. Few studies have been carried out on its prevalence in Asians. We conducted a prospective study on 60 patients with thromboembolism to determine its prevalence in our local population. The Factor V Leiden (VaQ506) mutation associated with this condition was detected by amplification of the Factor V gene by polymerase chain reaction (PCR) and digestion of the fragment with Mnl I. Three patients were found to be heterozygous for this mutation. None of the 3 patients had other concomitant hypercoagulable states. In addition, we studied the prevalence of this condition in Malays which was found to be 0.5%. Our study suggests that the incidence of APC-R is much lower here compared to the West.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  6. Normal values for total hand length, palm length and middle finger length in Malaysian newborns from 34-42 weeks of gestation
    Halder D, Dharap AS, Than M
    Anthropol Anz, 1999 Mar;57(1):69-75.
    PMID: 10320927
    Early identification of a syndrome at birth is of paramount importance for genetic counselling and possible prevention. Often malformation of the hands and fingers are cardinal manifestations of recognizable syndromes. As there are no published standards for hand and finger size for Malay newborn infants, this study was undertaken to establish normal values for hand, middle finger and palmar lengths, and their indices. A cross-sectional study was done on 509 consecutive newborn Malay babies between 34 and 42 weeks of gestation. Measurements were made on the right hand according to the recommended guidelines of Bergsma & Feingold (1975). The mean values for the measurements did not differ significantly between boys and girls, or change with gestation. For the whole group the mean value for total hand length was 64.4 +/- 3.42 mm, middle finger length 37.1 +/- 2.91 mm, palmar length 27.4 +/- 2.15 mm, finger index 0.425 +/- 0.03 and palmar index 0.58 +/- 0.03. A comparison with published measurements for newborns of different racial origin shows significant differences for the total hand length, middle finger length and palm length from Indian and Jewish infants, but not from Japanese infants. The indices were similar in Malay, Indian, Jewish and Japanese newborn infants.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  7. Lack of association between TPH2 gene polymorphisms with major depressive disorder in multiethnic Malaysian population
    Nazree NE, Loke AC, Zainal NZ, Mohamed Z
    Asia Pac Psychiatry, 2015 Mar;7(1):72-7.
    PMID: 24376086 DOI: 10.1111/appy.12118
    Numerous association studies of candidate genes studies with major depressive disorder (MDD) have been conducted for many years; however, the evidence of association between genes and the risk of developing MDD still remains inconclusive. In this study, we aimed to investigate the association between the tryptophan hydroxylase 2 (TPH2) gene and MDD in three ethnic groups (Malay, Chinese and Indian) within the Malaysian population.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  8. Fulltext Selected neuropeptide genes show genetic differentiation between Africans and non-Africans
    Tai KY, Wong K, Aghakhanian F, Parhar IS, Dhaliwal J, Ayub Q
    BMC Genet, 2020 03 14;21(1):31.
    PMID: 32171244 DOI: 10.1186/s12863-020-0835-8
    BACKGROUND: Publicly available genome data provides valuable information on the genetic variation patterns across different modern human populations. Neuropeptide genes are crucial to the nervous, immune, endocrine system, and physiological homeostasis as they play an essential role in communicating information in neuronal functions. It remains unclear how evolutionary forces, such as natural selection and random genetic drift, have affected neuropeptide genes among human populations. To date, there are over 100 known human neuropeptides from the over 1000 predicted peptides encoded in the genome. The purpose of this study is to analyze and explore the genetic variation in continental human populations across all known neuropeptide genes by examining highly differentiated SNPs between African and non-African populations.

    RESULTS: We identified a total of 644,225 SNPs in 131 neuropeptide genes in 6 worldwide population groups from a public database. Of these, 5163 SNPs that had ΔDAF |(African - non-African)| ≥ 0.20 were identified and fully annotated. A total of 20 outlier SNPs that included 19 missense SNPs with a moderate impact and one stop lost SNP with high impact, were identified in 16 neuropeptide genes. Our results indicate that an overall strong population differentiation was observed in the non-African populations that had a higher derived allele frequency for 15/20 of those SNPs. Highly differentiated SNPs in four genes were particularly striking: NPPA (rs5065) with high impact stop lost variant; CHGB (rs6085324, rs236150, rs236152, rs742710 and rs742711) with multiple moderate impact missense variants; IGF2 (rs10770125) and INS (rs3842753) with moderate impact missense variants that are in linkage disequilibrium. Phenotype and disease associations of these differentiated SNPs indicated their association with hypertension and diabetes and highlighted the pleiotropic effects of these neuropeptides and their role in maintaining physiological homeostasis in humans.

    CONCLUSIONS: We compiled a list of 131 human neuropeptide genes from multiple databases and literature survey. We detect significant population differentiation in the derived allele frequencies of variants in several neuropeptide genes in African and non-African populations. The results highlights SNPs in these genes that may also contribute to population disparities in prevalence of diseases such as hypertension and diabetes.

    Matched MeSH terms: European Continental Ancestry Group/genetics
  9. Fulltext Analysis of CTG repeat length variation in the DMPK gene in the general population and the molecular diagnosis of myotonic dystrophy type 1 in Malaysia
    Ambrose KK, Ishak T, Lian LH, Goh KJ, Wong KT, Ahmad-Annuar A, et al.
    BMJ Open, 2017 03 31;7(3):e010711.
    PMID: 28363916 DOI: 10.1136/bmjopen-2015-010711
    OBJECTIVE: The lack of epidemiological data and molecular diagnostic services in Malaysia has hampered the setting-up of a comprehensive management plan for patients with myotonic dystrophy type 1 (DM1), leading to delayed diagnosis, treatment and support for patients and families. The aim of this study was to estimate the prevalence of DM1 in the 3 major ethnic groups in Malaysia and evaluate the feasibility of a single tube triplet-primed PCR (TP-PCR) method for diagnosis of DM1 in Malaysia.

    DESIGN, SETTING AND PARTICIPANTS: We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion.

    OUTCOME MEASURES: The number of individuals not known to be affected by DM with (CTG)>18 was determined according to ethnic group and as a whole population. The χ2 test was performed to compare the distribution of (CTG)>18 with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation.

    RESULTS: Of the 754 chromosomes studied, (CTG)>18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation.

    CONCLUSIONS: The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries.

    Matched MeSH terms: European Continental Ancestry Group/genetics
  10. Fulltext Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry
    Moriyama T, Yang YL, Nishii R, Ariffin H, Liu C, Lin TN, et al.
    Blood, 2017 Sep 07;130(10):1209-1212.
    PMID: 28659275 DOI: 10.1182/blood-2017-05-782383
    Prolonged exposure to thiopurines (eg, mercaptopurine [MP]) is essential for curative therapy in acute lymphoblastic leukemia (ALL), but is also associated with frequent dose-limiting hematopoietic toxicities, which is partly explained by inherited genetic polymorphisms in drug metabolizing enzymes (eg, TPMT). Recently, our group and others identified germ line genetic variants in NUDT15 as another major cause of thiopurine-related myelosuppression, particularly in Asian and Hispanic people. In this article, we describe 3 novel NUDT15 coding variants (p.R34T, p.K35E, and p.G17_V18del) in 5 children with ALL enrolled in frontline protocols in Singapore, Taiwan, and at St. Jude Children's Research Hospital. Patients carrying these variants experienced significant toxicity and reduced tolerance to MP across treatment protocols. Functionally, all 3 variants led to partial to complete loss of NUDT15 nucleotide diphosphatase activity and negatively influenced protein stability. In particular, the p.G17_V18del variant protein showed extremely low thermostability and was completely void of catalytic activity, thus likely to confer a high risk of thiopurine intolerance. This in-frame deletion was only seen in African and European patients, and is the first NUDT15 risk variant identified in non-Asian, non-Hispanic populations. In conclusion, we discovered 3 novel loss-of-function variants in NUDT15 associated with MP toxicity, enabling more comprehensive pharmacogenetics-based thiopurine dose adjustments across diverse populations.
    Matched MeSH terms: European Continental Ancestry Group/genetics*
  11. 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
  12. Fulltext Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
    Zeng C, Guo X, Long J, Kuchenbaecker KB, Droit A, Michailidou K, et al.
    Breast Cancer Res, 2016 06 21;18(1):64.
    PMID: 27459855 DOI: 10.1186/s13058-016-0718-0
    BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.

    METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.

    RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P 

    Matched MeSH terms: European Continental Ancestry Group/genetics
  13. Fulltext Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk
    Yang Y, Wu L, Shu X, Lu Y, Shu XO, Cai Q, et al.
    Cancer Res, 2019 Feb 01;79(3):505-517.
    PMID: 30559148 DOI: 10.1158/0008-5472.CAN-18-2726
    DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 × 10-7. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. SIGNIFICANCE: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
    Matched MeSH terms: European Continental Ancestry Group/genetics*
  14. Fulltext Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes
    Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Electronic address: douglas.ruderfer@vanderbilt.edu, Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium
    Cell, 2018 Jun 14;173(7):1705-1715.e16.
    PMID: 29906448 DOI: 10.1016/j.cell.2018.05.046
    Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment.
    Matched MeSH terms: European Continental Ancestry Group/genetics
  15. Fulltext The haptoglobin 2-2 genotype is associated with inflammation and carotid artery intima-media thickness
    Dalan R, Liew H, Goh LL, Gao X, Chew DE, Boehm BO, et al.
    Diab Vasc Dis Res, 2016 09;13(5):373-6.
    PMID: 27190085 DOI: 10.1177/1479164116645247
    The haptoglobin 2-2 genotype is associated with atherosclerosis in type 2 diabetes mellitus. We examined the associations of the haptoglobin 2-2 genotype with C-reactive protein (high-sensitivity C-reactive protein) and carotid artery intima-media thickness, adjusting for age, gender, ethnicity, type 2 diabetes mellitus, smoking status, body mass index, blood pressure, glycated haemoglobin, non-high-density lipoprotein cholesterol and medications via logistic multivariate regression in 200 subjects (160 type 2 diabetes mellitus versus 40 healthy individuals). The prevalence of the haptoglobin 2-2 genotype was 58% (115/200), higher in the Indians than in Chinese (72% versus 45%, p = 0.001). Multivariate analysis showed that the haptoglobin 2-2 genotype was associated with high-sensitivity C-reactive protein [mean: 3.5 ± 3.9 versus 2.2 ± 2.6 mg/L (non-haptoglobin 2-2), p 
    Matched MeSH terms: European Continental Ancestry Group/genetics
  16. 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*
  17. 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*
  18. Association between functional polymorphisms in serotonin transporter gene (SLC6A4) and escitalopram treatment response in depressive patients in a South Indian population
    Mandal T, Bairy LK, Sharma PSVN
    Eur J Clin Pharmacol, 2020 Jun;76(6):807-814.
    PMID: 32253447 DOI: 10.1007/s00228-020-02866-4
    PURPOSE: Ethnicity plays a key role in deciding the direction of the association between serotonin transporter gene polymorphisms and treatment response of selective serotonin reuptake inhibitors (SSRIs). The present study explored the association of 5HTTLPR and 5HTTLPR-rs25531 polymorphisms with the treatment response of escitalopram in South Indian patients with major depressive disorder.

    METHODS: A total of 148 depressive patients receiving escitalopram 10-20 mg/day were genotyped for 5HTTLPR and rs25531 polymorphisms. Clinical assessment was done at baseline and after 4, 8, and 12 weeks using the 17-item Hamilton Depression Rating Scale (HDRS-17), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression Scale (CGI). At the end of week 12, patients were defined as responders and non-responders based on HDRS17 and MADRS scores. Chi-square test and logistic regression analysis were performed to investigate the genotypic influence on treatment response. Comparison of continuous variables among different groups was done using Student's t test or one-way ANOVA.

    RESULTS: Out of 148 study subjects, 65 (43.9%) were responders and 83 (56.08%) were non-responders. We observed a significant (p value group with better treatment response to escitalopram. The decline in HDRS17 and MADRS score from baseline was significantly higher (p value groups.

    CONCLUSION: Results suggest that 5HTTLPR and rs-25531 polymorphisms can influence escitalopram treatment response in depressive patients in a South Indian population, LL genotypes and LALA haplotypes being the predictors of better treatment response.

    Matched MeSH terms: European Continental Ancestry Group/genetics
  19. 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
  20. STR data for the AmpFlSTR Profiler loci from the three main ethnic population groups (Malay, Chinese and Indian) in Malaysia
    Lim KB, Jeevan NH, Jaya P, Othman MI, Lee YH
    Forensic Sci Int, 2001 Jun 01;119(1):109-12.
    PMID: 11348801
    Allele frequencies for the nine STRs genetic loci included in the AmpFlSTR Profiler kit were obtained from samples of unrelated individuals comprising 139-156 Malays, 149-153 Chinese and 132-135 Indians, residing in Malaysia.
    Matched MeSH terms: European Continental Ancestry Group/genetics*
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