15 results on '"Liuh Ling Goh"'
Search Results
2. Myeloid and lymphoid vacuolation in VEXAS syndrome
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Christian Aledia Gallardo, Ling Cao, Liuh Ling Goh, Ponnudurai Kuperan, Li Wearn Koh, Bingwen Eugene Fan, Kiat Hoe Ong, and Shang Ming Samuel Lee
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Male ,Pathology ,medicine.medical_specialty ,Myeloid ,business.industry ,Hereditary Autoinflammatory Diseases ,MEDLINE ,Hematology ,Syndrome ,medicine.anatomical_structure ,Text mining ,Vacuoles ,Medicine ,Humans ,Myeloid Cells ,Anemia, Macrocytic ,Lymphocytes ,business ,Aged - Published
- 2021
3. Assessment of droplet digital polymerase chain reaction for measuring BCR-ABL1 in chronic myeloid leukaemia in an international interlaboratory study
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Liam Whitby, Prasanthi Bhagavatula, Susan Rose, Andre B. Mulder, Elisabeth Oppliger Leibundgut, Edmond S. K. Ma, Sebastian Francis, Jacqueline Maier, Yogesh Shivakumar, Sara Galimberti, Lan Beppu, Josh Willoughby, Wing F Tang, Stéphanie Dulucq, Matthew Salmon, A. Pia Sanzone, Stuart Scott, Calogero Lauricella, Ashley Cartwright, Andrew D Chantry, Niels Pallisgaard, Hana Zizkova, Liuh Ling Goh, Carole Mauté, Nancy Boeckx, Chinh Duong, and Stem Cell Aging Leukemia and Lymphoma (SALL)
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Oncology ,Laboratory Proficiency Testing ,NILOTINIB ,bcr-abl ,Fusion Proteins, bcr-abl ,RELAPSE ,RTddPCR ,Bcr abl1 ,0302 clinical medicine ,hemic and lymphatic diseases ,Digital polymerase chain reaction ,Chronic ,610 Medicine & health ,CML ,Tumor ,Leukemia ,Reverse Transcriptase Polymerase Chain Reaction ,breakpoint cluster region ,Hematology ,BCR-ABL1 ,Quality ,external quality assessment (EQA) ,Asia ,Biomarkers, Tumor ,Europe ,HL-60 Cells ,Humans ,K562 Cells ,Laboratories, Clinical ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Linear Models ,North America ,Reagent Kits, Diagnostic ,Reproducibility of Results ,Real-time polymerase chain reaction ,030220 oncology & carcinogenesis ,Reagent Kits ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Coefficient of variation ,Chronic myeloid leukaemia ,IMATINIB ,03 medical and health sciences ,Clinical ,Internal medicine ,TRANSCRIPTS ,medicine ,Diagnostic ,Detection limit ,Science & Technology ,business.industry ,Fusion Proteins ,QUANTIFICATION ,Reverse transcriptase ,BCR-ABL Positive ,business ,Laboratories ,Biomarkers ,030215 immunology ,Myelogenous - Abstract
Measurement of BCR activator of RhoGEF and GTPase -ABL proto-oncogene 1, non-receptor tyrosine kinase (BCR-ABL1) mRNA levels by reverse transcription quantitative polymerase chain reaction (RTqPCR) has been critical to treatment protocols and clinical trials in chronic myeloid leukaemia; however, interlaboratory variation remains a significant issue. Reverse transcriptase droplet digital PCR (RTddPCR) has shown potential to improve testing but a large-scale interlaboratory study is required to definitively establish this. In the present study, 10 BCR-ABL1-positive samples with levels ranging from molecular response (MR)(1 center dot 0)-MR5 center dot 0 were tested by 23 laboratories using RTddPCR with the QXDX BCR-ABL %IS kit. A subset of participants tested the samples using RTqPCR. All 23 participants using RTddPCR detected BCR-ABL1 in all samples to MR4 center dot 0. Detection rates for deep-response samples were 95 center dot 7% at MR4 center dot 5, 78 center dot 3% at MR4 center dot 7 and 87 center dot 0% at MR5 center dot 0. Interlaboratory coefficient of variation was indirectly proportional to BCR-ABL1 level ranging from 29 center dot 3% to 69 center dot 0%. Linearity ranged from 0 center dot 9330 to 1 center dot 000 (average 0 center dot 9936). When results were compared for the 11 participants who performed both RTddPCR and RTqPCR, RTddPCR showed a similar limit of detection to RTqPCR with reduced interlaboratory variation and better assay linearity. The ability to detect deep responses with RTddPCR, matched with an improved linearity and reduced interlaboratory variation will allow improved patient management, and is of particular importance for future clinical trials focussed on achieving and maintaining treatment-free remission.
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- 2021
4. NLRP1, PTPN22 and PADI4 gene polymorphisms and rheumatoid arthritis in ACPA-positive Singaporean Chinese
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Liuh Ling, Goh, Mei Yun, Yong, Wei Qiang, See, Edward Yu Wing, Chee, Pei Qi, Lim, Ee Tzun, Koh, Khai Pang, Leong, and Bernard Yu-Hor, Thong
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Adult ,Male ,musculoskeletal diseases ,0301 basic medicine ,China ,medicine.medical_specialty ,Immunology ,Enzyme-Linked Immunosorbent Assay ,NLR Proteins ,Single-nucleotide polymorphism ,Real-Time Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Arthritis, Rheumatoid ,PTPN22 ,Young Adult ,03 medical and health sciences ,Protein-Arginine Deiminase Type 4 ,Rheumatology ,Risk Factors ,Internal medicine ,Genotype ,Humans ,Immunology and Allergy ,Medicine ,Genetic Predisposition to Disease ,Allele ,Adaptor Proteins, Signal Transducing ,Aged ,business.industry ,Protein Tyrosine Phosphatase, Non-Receptor Type 22 ,Middle Aged ,medicine.disease ,030104 developmental biology ,Case-Control Studies ,Rheumatoid arthritis ,PADI4 ,Cohort ,Protein-Arginine Deiminases ,Female ,Apoptosis Regulatory Proteins ,business - Abstract
Studies have shown that the genetic risk factors for rheumatoid arthritis (RA) differ substantially between Asian and Caucasian populations. Even among Asian populations, the genetic contributions of NLRP1, PTPN22 and PADI4 have been controversial. Consequently, we sought to address these separate findings and determine whether any of these proposed risk variants are associated with RA susceptibility, onset, DAS activity and erosion in a Singaporean Chinese cohort. We genotyped five SNPs within NLRP1 (rs878329 and rs6502867), PTPN22 (rs2488457 and rs6665194), and PADI4 (rs2240340) in 500 anti-cyclic citrullinated peptide antibody-positive (ACPA) patients with RA and 500 healthy controls using TaqMan assays. The CC genotype of NLRP1 rs878329 and TT genotype of PADI4 rs2240340 were associated with RA susceptibility. The risk association of the T allele of PADI4 rs2240340 with RA was confirmed through a meta-analysis based on previous reports in Asian populations. The GG genotype of PTPN22 rs6665194 (−3508A>G) was associated with significantly reduced risk of RA. No significant association was found for NLRP1 rs6502867 T/C and PTPN22 rs2488457 G/C polymorphisms. None of the five SNPs was associated with RA’s clinical features. This work supports the association of the T allele of PADI4 rs2240340 with RA in Asians. The roles of NLRP1 rs878329 G/C and PTPN22 rs6665194 A/G polymorphisms were demonstrated for the first time. We also propose rs6665194 to be a promising candidate for RA risk evaluation between ethnicities.
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- 2017
5. CYP2C19 phenotype in South-East Asian Acute Coronary Syndrome patients and impact on major adverse cardiovascular events
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Liuh Ling Goh, Han Kiat Ho, Doreen Su-Yin Tan, Hean Yee Ong, Jianjun Liu, Michael Winther, Jernice Wan Xin Aw, and Eric Wee
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Male ,medicine.medical_specialty ,Acute coronary syndrome ,Prasugrel ,Genotype ,medicine.medical_treatment ,Hemorrhage ,CYP2C19 ,030226 pharmacology & pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Percutaneous Coronary Intervention ,Asian People ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,cardiovascular diseases ,030212 general & internal medicine ,Acute Coronary Syndrome ,Aged ,Retrospective Studies ,Pharmacology ,business.industry ,Percutaneous coronary intervention ,Middle Aged ,Clopidogrel ,medicine.disease ,Cytochrome P-450 CYP2C19 ,Phenotype ,Cardiovascular Diseases ,Pharmacogenetics ,Female ,business ,Prasugrel Hydrochloride ,Mace ,Platelet Aggregation Inhibitors ,Cohort study ,medicine.drug - Abstract
WHAT IS KNOWN AND OBJECTIVE Several Caucasian cohort studies have associated at least one loss-of-function CYP2C19 on Clopidogrel (LoF-Clopidogrel) with major adverse cardiovascular events (MACE), and only a couple have used Clinical Pharmacogenetics Implementation Consortium (CPIC® ) phenotype grouping to study the associations. We primarily aimed to study the impact of use of platelet reactivity testing to escalate antiplatelet therapy and secondarily to study the association of CPIC phenotype with MACE outcomes in South-East Asian Acute Coronary Syndrome (ACS) subjects. METHOD A retrospective genotype study was performed on 238 percutaneous coronary intervention subjects, originally planned for escalation of antiplatelets using platelet reactivity testing. RESULTS AND DISCUSSION There was no difference in MACE between the switched and unswitched groups; however, 'all bleeds' and 'clinically significant bleeds' (CSB) were statistically higher in the patients who were switched to prasugrel. The subgroup of patients who remained on clopidogrel (n = 199) were analysed using phenotype categories and MACE. Eleven percent (11.4%) of CYP2C19 poor metabolizers (PM) suffered MACE, compared with 1.3% of extensive metabolizers (EM). LoF-Clopidogrel patients are significantly more likely to experience MACE compared with non-LoF subjects (8.0% vs 5.4%, P: .041). WHAT IS NEW AND CONCLUSION In our multivariate analysis, LoF-Clopidogrel, malay ethnicity, diabetics and use of proton pump inhibitors were independent predictors of MACE. There were numerically more bleeds in LoF subjects who were on prasugrel compared with Clopidogrel (23.5% vs 11%, P = .082). Our data corroborate with current findings on platelet reactivity testing, suggesting that the assay would not be sensitive enough to pick up sufficient 'at-risk' subjects as compared to the use of CYP2C19 genotyping.
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- 2019
6. The haptoglobin 2-2 genotype is associated with inflammation and carotid artery intima-media thickness
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Bernhard O. Boehm, Melvin Khee-Shing Leow, Daniel Ek Chew, Liuh Ling Goh, Rinkoo Dalan, Huiling Liew, and Xiao Gao
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Carotid Artery Diseases ,Male ,Endocrinology, Diabetes and Metabolism ,Carotid arteries ,carotid atherosclerosis ,Pilot Projects ,030204 cardiovascular system & hematology ,Haptoglobin polymorphism ,Carotid Intima-Media Thickness ,0302 clinical medicine ,Gene Frequency ,Risk Factors ,Genotype ,polycyclic compounds ,skin and connective tissue diseases ,Singapore ,biology ,Brief Report ,Haptoglobin ,food and beverages ,Middle Aged ,Phenotype ,Female ,medicine.symptom ,Inflammation Mediators ,Cardiology and Cardiovascular Medicine ,Adult ,medicine.medical_specialty ,China ,India ,Inflammation ,White People ,C-reactive protein ,03 medical and health sciences ,Asian People ,Predictive Value of Tests ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Association Studies ,Haptoglobins ,business.industry ,Malaysia ,Type 2 Diabetes Mellitus ,medicine.disease ,Endocrinology ,Cross-Sectional Studies ,Intima-media thickness ,Case-Control Studies ,biology.protein ,business ,030217 neurology & neurosurgery - Abstract
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
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- 2016
7. Abstract 4600: Germline homologous recombination deficiency pathway defects in a multi-ethnic East Asian, Southeast Asian and South Asian cancer patient cohort
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Ann Sg Lee, Wei Lim Chia, Min-Han Tan, Hao Chen, Matthew Myint, Choudhury Yukti, Ru Jin Tay, Jens Samol, and Liuh Ling Goh
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Oncology ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,Cancer prevention ,medicine.diagnostic_test ,business.industry ,PALB2 ,Population ,Cancer ,Gene mutation ,medicine.disease ,Southeast asian ,Internal medicine ,medicine ,Family history ,business ,education ,Genetic testing - Abstract
Introduction There is limited diversity in current hereditary multi-gene testing data-sets, leading to greater challenges in accurate variant classification. To address this, a collaboration between 3 Singapore-based healthcare organizations (Tan Tock Seng Hospital, National Cancer Centre Singapore and Lucence Diagnostics) pooled results from patients of East Asian, Southeast Asian and South Asian ancestry, representing over 60% of the world's population. We hypothesized that a multi-ethnic collaboration would provide deeper understanding of cancer predisposition genes, particularly in terms of novel variants. Methods A total of 704 cancer patients of multi-ethnic Asian (SE Asian, East Asian and South Asian) ethnicity with either a history of breast, ovarian, pancreatic or prostate cancer, were tested with multi-gene panels. All patients were tested by multi-gene testing, including but not limited to BRCA1/2, PALB2 and ATM. In addition to genetic testing, the family histories of the patients were collected. All variants were classified by ACMG criteria. Chi-square testing was used for statistical analysis. Results Three sites (TTSH, NCCS, and Lucence) pooled patients selected for breast (n=458), ovarian (n=176), pancreatic (n=61) and prostate cancer (n=25). The mean and median ages were 44.9 years and 43 years, respectively. Of the 704 patients, 209 had a history of cancer in their first degree relatives, 432 did not and 63 patients did not know of any cancers in their first degree relatives. 122 of 704 patients (17.33%) had pathogenic/likely pathogenic variants in any tested risk-related gene, of which 86 were in BRCA1/2, 11 in PALB2 and 4 in ATM. Some variants were detected in more than one patient. 212 of 704 patients (30.1%) had VUSs detected in any tested risk-related gene, with 32.1% in BRCA1/2. There was a positive association between multiple-cancer status and pathogenic variants (9/22 vs 113/682, p = 0.007). Most notably, among the unique pathogenic/likely pathogenic variants in BRCA1, BRCA2, PALB2 and ATM, 10.64% (5/47), 12.9% (4/31), 30% (3/10) and 25% (1/4) respectively were novel variants, not previously reported in ClinVar (Dec 2019). Conclusion To our knowledge, this is the largest regional multi-ethnic cohort of patients with breast, ovarian, pancreatic and prostate cancer undergoing comprehensive genetic testing. Only one third of patients reported a first-degree family history suggesting that testing ought to be performed if clinical suspicion is high. Notably, 14.1% of BRCA1/BRCA2/PALB2/ATM pathogenic/likely pathogenic variants detected in our cohort were novel variants, not hitherto published in ClinVar. In conclusion, this collaboration demonstrates that testing of Asian patients can enrich global understanding of cancer predisposition gene mutations. This will improve cancer prevention, surveillance, and treatment selection for cancer patients, such as the use of PARP inhibitors for genetic defects of DNA repair. Citation Format: Jens Samol, Wei Lim Chia, Liuh Ling Goh, Matthew Myint, Min-Han Tan, Ru Jin Tay, Hao Chen, Yukti Choudhury, Ann SG Lee. Germline homologous recombination deficiency pathway defects in a multi-ethnic East Asian, Southeast Asian and South Asian cancer patient cohort [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4600.
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- 2020
8. Total Oxidative Index Is Associated with Glycated Hemoglobin, Low-Grade Inflammation, and Non-HDL Cholesterol in Type 2 Diabetes
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Rinkoo Dalan, Xin Tang, Bernhard O. Boehm, Daniel E.K. Chew, and Liuh Ling Goh
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medicine.medical_specialty ,Cholesterol ,Endocrinology, Diabetes and Metabolism ,Type 2 Diabetes Mellitus ,Inflammation ,Type 2 diabetes ,Oxidative phosphorylation ,medicine.disease ,medicine.disease_cause ,chemistry.chemical_compound ,Blood pressure ,Endocrinology ,chemistry ,Internal medicine ,Internal Medicine ,medicine ,Glycated hemoglobin ,medicine.symptom ,Oxidative stress - Abstract
Objectives: To study associations of established cardiovascular risk factors, inflammation and carotid artery intima-media thickness (CIMT) with oxidative stress in type 2 diabetes mellitus (T2DM). Methods: We recruited 343 T2DM subjects from the three main ethnic groups in Singapore (Chinese: 196, Indians: 106, Malays: 41; Age: 54.7±10.4 years; Males: 46%). Measurements: Demographics, BMI, blood pressure, HbA1c, glucose and lipids; CIMT and C-reactive protein (hsCRP). Derivatives of reactive oxygen metabolites (dROMS) and total anti-oxidant status (TAC) was estimated by the automated clinical chemistry analyser (Diacron, Italy). The total oxidative index (OXY) was calculated as the difference between standardised dROMS and TAC values. The relationship between OXY, dROMS and TAC as dependent variable and age, gender, ethnicity, BMI, blood pressure, HbA1c, fasting lipids, log CRP and CIMT as co-variates was assessed using multiple regression analysis. Associations with gender and ethnicity were assessed by student’s t test and Kruskal Wallis test respectively. Results: The mean OXY was higher in the females (0.2±1.3) compared to the males (0.2±1.0); p Conclusions: In T2DM, total oxidative stress is a function of HbA1c, non-HDL-Cholesterol and low-grade inflammation. HbA1c and inflammation increase reactive oxygen metabolites, whereas non-HDL cholesterol decreases the anti-oxidant potential. The mechanisms of oxidative stress generation, in particular in various ethnic groups, needs to be studied further. Disclosure R. Dalan: None. L. Goh: None. X. Tang: None. D.E.K. Chew: None. B. Boehm: None.
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- 2018
9. Letter by Aw et al Regarding Article, 'Clinical Outcomes and Sustainability of Using CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention'
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Jernice Wan Xin Aw, Liuh Ling Goh, and Doreen Su-Yin Tan
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0301 basic medicine ,medicine.medical_specialty ,Prasugrel ,Genotype ,medicine.medical_treatment ,MEDLINE ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Percutaneous Coronary Intervention ,0302 clinical medicine ,medicine ,Aspirin ,Prasugrel Hydrochloride ,business.industry ,Percutaneous coronary intervention ,General Medicine ,Clopidogrel ,Cytochrome P-450 CYP2C19 ,030104 developmental biology ,Cohort ,Emergency medicine ,Platelet aggregation inhibitor ,business ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
We read the recent studies by Lee et al1 and the IGNITE network (Implementing Genomics in Practice) with much interest and wish to share findings from our cohort of 247 Asians in Khoo Teck Puat Hospital, Singapore. To our knowledge, we are the first Asian group to demonstrate similar interventional cohort findings as those of Lee et al1 and Cavallari et al from the IGNITE network.2 We conducted a single-center, prospective, open label study in 247 Asian patients who underwent percutaneous coronary intervention and received dual antiplatelet therapy consisting of aspirin and clopidogrel. At the time of design, we intended to switch subjects with high-on-treatment response from clopidogrel to prasugrel. Additional blood samples were collected for genotyping. High-on-treatment …
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- 2018
10. The Cholesterol Efflux Capacity (Cec) Correlates With Oxidative Stress In Type 2 Diabetes Mellitus
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L.X.G. Toh, A. Seneviratna, Rinkoo Dalan, E.K.D. Chew, X. Lian, Bernhard Otto Boehm, C.J. Seow, S.X.S. Chua, Huiling Liew, and Liuh Ling Goh
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medicine.medical_specialty ,business.industry ,Cholesterol ,Type 2 Diabetes Mellitus ,medicine.disease_cause ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Medicine ,Efflux ,Cardiology and Cardiovascular Medicine ,business ,Oxidative stress - Published
- 2019
11. Endothelial cell apoptosis correlates with low haptoglobin concentrations in diabetes
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Kathy Qian Luo, Sun Bing, Rinkoo Dalan, Xiaofeng Liu, and Liuh Ling Goh
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0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,Apoptosis ,Pilot Projects ,030204 cardiovascular system & hematology ,medicine.disease_cause ,haptoglobin genotype ,0302 clinical medicine ,Lab-On-A-Chip Devices ,Genotype ,polycyclic compounds ,skin and connective tissue diseases ,Cells, Cultured ,biology ,medicine.diagnostic_test ,diabetes ,Haptoglobin ,food and beverages ,haptoglobin ,Phenotype ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,Inflammation ,03 medical and health sciences ,Western blot ,Internal medicine ,Diabetes mellitus ,Microchip Analytical Procedures ,Internal Medicine ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,Endothelial cell apoptosis ,Chi-Square Distribution ,Haptoglobins ,business.industry ,Case-control study ,medicine.disease ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Immunology ,Multivariate Analysis ,biology.protein ,Brief Reports ,business ,Oxidative stress ,Biomarkers - Abstract
Objective: The haptoglobin 2-2 genotype is associated with lower haptoglobin concentrations and atherosclerosis in diabetes. Endothelial cell apoptosis contributes significantly to atherosclerosis. We studied endothelial cell apoptosis in diabetes patients with haptoglobin 2-2 and non-haptoglobin 2-2 genotype. Approach and results: We pooled plasma from 10 patients with haptoglobin 2-2 and non-haptoglobin 2-2 genotype and quantified endothelial cell apoptosis using a hemodynamic lab-on-chip system. Then, we conducted similar experiments on individual diabetes plasma samples with the haptoglobin 2-2 (n = 20) and non-haptoglobin 2-2 genotype (n = 20). Haptoglobin beta concentrations were measured by Western blot analysis. We looked for association with demographic, metabolic variables, inflammation and oxidative stress. In pooled plasma, endothelial cell apoptosis was higher in haptoglobin 2-2 group (haptoglobin 2-2: 23.18% vs non-haptoglobin 2-2:15.32%). In individual samples, univariate analysis showed that endothelial cell apoptosis correlated with haptoglobin beta concentration [β = −10.29 (95% confidence interval: −13.44, −7.14), p 0.05). Conclusion: These results show that regardless of the haptoglobin genotype, haptoglobin is associated with prevention of endothelial cell apoptosis in diabetes.
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- 2017
12. Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore
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Degang Wu, Jinzhuang Dou, Xiaoran Chai, Claire Bellis, Andreas Wilm, Chih Chuan Shih, Wendy Wei Jia Soon, Nicolas Bertin, Clarabelle Bitong Lin, Chiea Chuen Khor, Michael DeGiorgio, Shanshan Cheng, Li Bao, Neerja Karnani, William Ying Khee Hwang, Sonia Davila, Patrick Tan, Asim Shabbir, Angela Moh, Eng-King Tan, Jia Nee Foo, Liuh Ling Goh, Khai Pang Leong, Roger S.Y. Foo, Carolyn Su Ping Lam, Arthur Mark Richards, Ching-Yu Cheng, Tin Aung, Tien Yin Wong, Huck Hui Ng, Jianjun Liu, Chaolong Wang, Matthew Andrew Ackers-Johnson, Edita Aliwarga, Kenneth Hon Kim Ban, Denis Bertrand, John C. Chambers, Dana Leng Hui Chan, Cheryl Xue Li Chan, Miao Li Chee, Miao Ling Chee, Pauline Chen, Yunxin Chen, Elaine Guo Yan Chew, Wen Jie Chew, Lynn Hui Yun Chiam, Jenny Pek Ching Chong, Ivan Chua, Stuart A. Cook, Wei Dai, Rajkumar Dorajoo, Chuan-Sheng Foo, Rick Siow Mong Goh, Axel M. Hillmer, Ishak D. Irwan, Fazlur Jaufeerally, Asif Javed, Justin Jeyakani, John Tat Hung Koh, Jia Yu Koh, Pavitra Krishnaswamy, Jyn Ling Kuan, Neelam Kumari, Ai Shan Lee, Seow Eng Lee, Sheldon Lee, Yen Ling Lee, See Ting Leong, Zheng Li, Peter Yiqing Li, Jun Xian Liew, Oi Wah Liew, Su Chi Lim, Weng Khong Lim, Chia Wei Lim, Tingsen Benson Lim, Choon Kiat Lim, Seet Yoong Loh, Au Wing Lok, Calvin W.L. Chin, Shivani Majithia, Sebastian Maurer-Stroh, Wee Yang Meah, Shi Qi Mok, Niranjan Nargarajan, Pauline Ng, Sarah B. Ng, Zhenyuan Ng, Jessica Yan Xia Ng, Ebonne Ng, Shi Ling Ng, Simon Nusinovici, Chin Thing Ong, Bangfen Pan, Vincent Pedergnana, Stanley Poh, Shyam Prabhakar, Kumar M. Prakash, Ivy Quek, Charumathi Sabanayagam, Wei Qiang See, Yee Yen Sia, Xueling Sim, Wey Cheng Sim, Jimmy So, Dinna K.N. Soon, E. Shyong Tai, Nicholas Y. Tan, Louis C.S. Tan, Hong Chang Tan, Wilson Lek Wen Tan, Moses Tandiono, Amanda Tay, Sahil Thakur, Yih Chung Tham, Zenia Tiang, Grace Li-Xian Toh, Pi Kuang Tsai, Lavanya Veeravalli, Chandra S. Verma, Ling Wang, Min Rui Wang, Wing-Cheong Wong, Zhicheng Xie, Khung Keong Yeo, Liang Zhang, Weiwei Zhai, Yi Zhao, Cardiovascular Centre (CVC), Lee Kong Chian School of Medicine (LKCMedicine), and School of Biological Sciences
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Male ,medicine.medical_specialty ,Demographic history ,Population ,Genome-wide association study ,HAPLOTYPE ,Biology ,VARIANTS ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,ANCESTRY ESTIMATION ,03 medical and health sciences ,0302 clinical medicine ,Whole-genome Sequencing ,Asian People ,HISTORY ,medicine ,Humans ,WIDE ASSOCIATION ,Medicine [Science] ,Selection, Genetic ,education ,ADAPTATION ,030304 developmental biology ,Whole genome sequencing ,Singapore ,0303 health sciences ,Genetic diversity ,education.field_of_study ,Whole Genome Sequencing ,Asian Populations ,Genome, Human ,Malaysia ,Human genetics ,GENOTYPE ,MODEL ,Genetics, Population ,Evolutionary biology ,Medical genetics ,Female ,HEALTH ,HUMAN-EVOLUTION ,030217 neurology & neurosurgery ,Imputation (genetics) - Abstract
Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Accepted version We acknowledge H.M. Kang, S. Das, A. Tan, F. Zhang, J. Terhorst, P.-R. Loh, and G. Hellenthal for helpful discussions and support from all participants and clinical research coordinators of the contributing cohorts and studies: the TTSH Healthy Control Workgroup, the SEED cohort, the Asian Sudden Cardiac Death in Heart Failure Study, the Singapore Heart Failure Outcomes and Phenotypes (SHOP) cohort, the Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT), the Parkinson’s Disease Study, the Peranakan Genome Study, the Platinum Asian Genomes Project, the Bariatric Surgery Study, the National Heart Centre Singapore Biobank and SingHEART cohorts, and the GUSTO and S-PRESTO study groups. This study was supported by Singapore’s A*STAR (core funding and IAF-PP H17/01/a0/007), BMRC (SPF2014/001, SPF2013/002, SPF2014/003, SPF2014/004, and SPF2014/005), NMRC (CIRG/1371/2013, CIRG/1417/2015, CIRG/1488/ 2018, CSA-SI/0012/2017, CG/017/2013, CG/M006/2017_NHCS, TCR/013- NNI/2014, STaR/0011/2012, STaR2013/001, STaR/014/2013, STaR/0026/ 2015, TCR/006-NUHS/2013, TCR/012-NUHS/2014, TCR/004-NUS/2008, TCR/012-NUHS/2014, and center grants 2010-13 and 2013-2017), NRF (NRFF2016-03), National University of Singapore, SingHealth and DukeNUS, and Alexandra Health small innovative grant SIGII/15203 and funding from Huazhong University of Science and Technology, the Tanoto Foundation, the Lee Foundation, the Boston Scientific Investigator Sponsored Research Program and Bayer, the NSF (DEB-1753489), and the Alfred P. Sloan Foundation. The computation was partially performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg).
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- 2019
13. Impact Of Vitamin E Supplementation On Vascular Function In Patients With Type 2 Diabetes Mellitus Stratified By Haptoglobin Genotype (Evas Trial): A Randomized Controlled Trial
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D. Chew Ek, X. Lian, C.J. Seow, A. Seneviratna, Rinkoo Dalan, Bernhard Otto Boehm, Liuh Ling Goh, Huiling Liew, and M. Leow Ks
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medicine.medical_specialty ,biology ,business.industry ,Haptoglobin ,Vitamin e supplementation ,Type 2 Diabetes Mellitus ,Gastroenterology ,law.invention ,Randomized controlled trial ,law ,Internal medicine ,Genotype ,biology.protein ,Medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business ,Vascular function - Published
- 2019
14. The GG genotype of vitamin D metabolism-related gene DHCR7 rs12785878 is more prevalent in the Indians and associated with higher oxidative stress index in Singapore
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Huiling Liew, B.O. Boehm, X. Gao, Liuh Ling Goh, Daniel Ek Kwang Chew, and Rinkoo Dalan
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Genetics ,medicine.medical_specialty ,Vitamin D metabolism ,Index (economics) ,business.industry ,medicine.disease_cause ,Endocrinology ,Internal medicine ,Genotype ,medicine ,Related gene ,Cardiology and Cardiovascular Medicine ,business ,Oxidative stress - Published
- 2016
15. Evaluation of oxidative stress index and its correlation with traditional cardiovascular risk factors, inflammation and carotid intima media thickness in diabetes and healthy subjects
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Daniel Ek Kwang Chew, X. Gao, Melvin Khee-Shing Leow, Bernhard Otto Boehm, Rinkoo Dalan, Huiling Liew, and Liuh Ling Goh
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medicine.medical_specialty ,Index (economics) ,business.industry ,Cardiovascular risk factors ,Healthy subjects ,Inflammation ,medicine.disease ,medicine.disease_cause ,Correlation ,Intima-media thickness ,Diabetes mellitus ,Internal medicine ,Cardiology ,Medicine ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Oxidative stress - Published
- 2016
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