瀏覽人氣：3,050

柯毓麟 醫師

最高學歷：台大臨床醫學研究所博士

研究領域：台灣人心血管代謝相關因子及疾病之遺傳決定因子、台灣人心血管疾病之預後因子

分機：5355

電子信箱：yulinkotco@tzuchi.com.tw

https://orcid.org/0000-0002-8218-6827

  • 台灣人心血管代謝相關因子及疾病之遺傳決定因子。
  • 台灣人心血管疾病之預後因子。

參考著作：

  1. Er LK, Wu S, Hsu LA, Teng MS, Sun YC, Ko YL*. Pleiotropic Associations of RARRES2 Gene Variants and Circulating Chemerin Levels: Potential Roles of Chemerin Involved in the Metabolic and Inflammation-Related Diseases. Mediators of Inflammation 2018, Article ID 4670521.
  2. Teng MS, Hsu LA, Juan SH, Lin WC, Lee MC, Su CW, Wu S*, Ko YL*. A GDF15 30 UTR variant, rs1054564, results in allele-specific translational repression of GDF15 by hsa-miR-1233-3p. PLoS One. 2017 Aug 14;12(8):e0183187.
  3. Ko YL*, Hsu LA, Wu S, Teng MS, Chou HH. CRP and SAA1 haplotypes are associated with both C-reactive protein and serum amyloid A levels: Role of suppression effects. Mediators Inflamm. 2016;2016:5830361.
  4. Teng MS, Hsu LA, Wu S, Chou HH, Chang CJ, Sun YZ, Juan SH*, Ko YL*. Mediation analysis reveals a sex-dependent association between ABO gene variants and TG/HDL-C ratio that is suppressed by sE-selectin level. Atherosclerosis. 2013 Jun;228(2):406-12.
  5. Wu S, Hsu LA, Teng MS, Lin JF, Chou HH, Lee MC, Wu YM, Su CW, Ko YL*. Interactive effects of C-reactive protein levels on the association between APOE variants and triglyceride levels in a Taiwanese population. Lipids Health Dis. 2016 May 13;15(1) 94.

參考著作：

  1. Hsu LA, Wu S, Juang JJ, Chiang FT, T MS, Lin JF, Huang HL, Ko YL*. Growth differentiation factor 15 may predict mortality of peripheral and coronary artery diseases and correlate with their risk factors. Mediators Inflamm. 2017;2017:9398401.
  2. Lin JF, Wu S, Jimmy Juang JM, Chiang FT, Hsu LA, Teng MS, Cheng ST, Huang HL, Sun YC, Liu PY, Ko YL*. IL1RL1 single nucleotide polymorphism predicts sST2 level and mortality in coronary and peripheral artery disease. Atherosclerosis. 2017 Feb;257:71-77.
  3. Wu S, Hsu LA, Cheng ST, Teng MS, Yeh CH, Sun YC, Huang HL, Ko YL*. Circulating YKL-40 level, but not CHI3L1 gene variants, is associated with atherosclerosis-related quantitative traits and the risk of peripheral artery disease. Int J Mol Sci. 2014 Dec 4;15(12):22421-37.
  4. Leay Kiaw Er, Lung-An Hsu, Jyh-Ming Jimmy Juang, Fu-Tien Chiang, Ming-Sheng Teng, I-Shiang Tzeng, Semon Wu, Jeng-Feng Lin, Yu-Lin Ko*. Circulating Chemerin Levels, but not the RARRES2 Polymorphisms, Predict the Long-Term Outcome of Angiographically Confirmed Coronary Artery Disease. Int J Mol Sci. 2019 Mar 7;20(5):1174.
  5. Liao YH, Teng MS, Jhang JY, Chiang FT, Er LK, Wu S, Ko YL*. Genetic determinants of circulating galectin-3 levels in patients with coronary artery disease.Mol Genet Genomic Med.2020 Sep;8(9):e1370.
研究主題:後GWAS時代的功能基因組學在心血管代謝疾病之角色

研究方向簡述: 近二十多年來我們的研究團隊利用候選基因模式持續的探討台灣人心血管及代謝因子之遺傳決定因素，所分析超過30種臨床表現型，生物標記與心血管疾病。自2005起，無假設的全基因組關聯研究(GWAS)已成功聯結>5000項研究中大量單核苷酸多態性(SNP)位點與>10,000種複雜人類特徵和多因子疾病之相關性。使用來自台灣人體生物資料庫的基因大數據，我們以GWAS、區域關聯分析和孟德爾隨機化(MR)研究方法揭示許多GWAS先導SNP在心血管代謝疾病及其相關之複雜性狀與生物標記中的角色，其中多個候選基因變異屬於未曾報告且為亞洲人獨特的非同義突變或調節區域SNP。這些研究結果自1996以後迄今我們團隊共刊登超過50篇基因與生物標記相關性研究原著論文。然而GWAS研究結果中高達95%具顯著統計訊息的疾病相關變異於非編碼區域(non-coding region)，這對如何闡明其致病基因和相關機轉提出了相當大之挑戰。最近快速增長的多個功能基因組學特定計算工具及網路平台模式，如共定位(colocalization)研究模式，已經成功顯示如何使用GWAS基因變異研究結果以找到候選致病基因和基因變異之方法。為求建立後GWAS時代的功能基因組學在心血管代謝疾病之角色，我們擬使用許多最近新開發的計算工具及網路平台，例如FUMA（用於SNP到基因和基因到功能的評估）、THISTLE（用於sQTL）、3D Genome Browser (用於3D染色質相互作用分析)、ezQTL（用於共定位）、PoPS (用於基因到複雜性狀和疾病）、cS2G (用於SNP到致病基因) 和MRlocus（用於MR和共定位的組合）等研究模式來闡明我們新發現的GWAS基因變異在功能上的角色，並進一步整合MR和基因優先策略（包括共定位研究）的生物信息學方法及基因功能性測試，以達到候選基因及其致病基因變異的建立(如下圖所示)。短期目標擬運用台灣人體生物資料庫的基因、問卷與血液檢體分析資料，持續找尋台灣人(或亞洲人)獨特之基因變異，建立更完整之基因圖譜。中期目標擬利用功能基因組學計算工具及網路平台與功能性測試建立所找到之獨特基因變異功能上的角色；長期目標希望結合健保資料庫以用於前瞻性研究，並用以預測心血管代謝相關疾病之發生及其預後。

參考著作：
  1. Ming-Sheng Teng†, Kuan-Hung Yeh†, Lung-An Hsu, Hsin-Hua Chou, Leay Kiaw Er, Semon Wu, Yu-Lin Ko*. Differential Effects of ABCG5/G8 Gene Region Variants on Lipid Profile, Blood Pressure Status, and Gallstone Disease History in Taiwan. Genes 2023, 14(3), 754.
  2. Shih-Jung Jang#, Wei-Lun Tuan#, Lung-An Hsu, Leay-Kiaw Er, Ming-Sheng Teng,Semon Wu, Yu-Lin Ko*. Pleiotropic Effects of APOB Variants on Lipid Profiles, metabolic Syndrome, and the Risk of Diabetes Mellitus. Int J Mol Sci. 2022 Nov 29;23(23):14963.
  3. Kuan-Hung Yeh#, Lung-An Hsu#, Jyh-Ming Jimmy Juang, Fu-Tien Chiang,Ming-Sheng Teng, I-Shiang Tzeng, Semon Wu, Jeng-Feng Lin, Yu-Lin Ko*. Circulating serum amyloid A levels but Not SAA1 variants predict long-term outcomes of angiographically confirmed coronary artery disease. Tzu Chi Medical Journal 2022; 34 (4) 423-433.
  4. Lung-An Hsu, Ming-Sheng Teng, Semon Wu, Hsin-Hua Chou, Yu-Lin Ko*. Common and Rare PCSK9 Variants Associated withLow-Density Lipoprotein Cholesterol Levels and the Risk of Diabetes Mellitus: A Mendelian Randomization Study. Int. J. Mol. Sci. 2022, 23(18), 10418.
  5. Kuan-Hung Yeh, Hsiang-Lin Wan, Ming-Sheng Teng, Hsin-Hua Chou, Lung-An Hsu, Yu-Lin Ko*. Genetic Variants at the APOE Locus Predict Cardiometabolic Traits and Metabolic Syndrome: A Taiwan Biobank Study. Genes (Basel). 2022 Jul 29;13(8):1366.
  6. Yu-Lin Ko*. Genetics of hyperuricemia and gout: Insight from Mendelian randomization studies. Tzu Chi Medical Journal 2022; 34(3): 261‑269.
  7. Hsin-Hua Chou, Lung-An Hsu, Jyh-Ming Jimmy Juang, Fu-Tien Chiang, Ming-Sheng Teng, Semon Wu, Yu-Lin Ko*. Synergistic Effects of Weighted Genetic Risk Scores and Resistin and sST2 Levels on the Prognostication of Long-Term Outcomes in Patients with Coronary Artery Disease. Int J Mol Sci. 2022 Apr 13;23(8):4292.
  8. Semon Wu, Lung-An Hsu, Ming-Sheng Teng, Hsin-Hua Chou, Yu-Lin Ko*. Differential Genetic and Epigenetic Effects of the KLF14 Gene on Body Shape Indices and Metabolic Traits. Int J Mol Sci. 2022 Apr 9;23(8):4165.
  9. Kuan-Hung Yeh, Lung-An Hsu, Ming-Sheng Teng, Semon Wu, Hsin-Hua Chou, Yu-Lin Ko*. Pleiotropic Effects of Common and Rare GCKR Exonic Mutations on Cardiometabolic Traits. Genes (Basel). 2022 Mar 10;13(3):491
  10. Kuan-Hung Yeh, Lung-An Hsu, Jyh-Ming Jimmy Juang, Fu-Tien Chiang, Ming-Sheng Teng, I-Shiang Tzeng, Semon Wu, Jeng-Feng Lin, Yu-Lin Ko*. Circulating serum amyloid A levels but Not SAA1 variants predict long-term outcomes of angiographically confirmed coronary artery disease. Tzu Chi Med J. 2022 Jan 31;34(4):423-433.
  11. Ming-Sheng Teng, Lung-An Hsu, Semon Wu, I-Shiang Tzeng, Hsin-Hua Chou, Yu-Lin Ko*. Genome-wide association study revealed novel candidate gene loci associated with soluble E-selectin levels in a Taiwanese population. Atherosclerosis, 2021 Nov;337:18-26.
  12. Er LK, Wu S, Cheng T, Ko YL*, Teng MS*. Genome-Wide Association Study on Adiponectin-Mediated Suppression of HDL-C Levels in Taiwanese Individuals Identifies Functional Haplotypes in CDH13. Genes (Basel). 2021 Oct 7;12(10):1582.
  13. Ming-Sheng Teng, Semon Wu, Lung-An Hsu, Hsin-Hua Chou, Yu-Lin Ko*. Pleiotropic Effects of Functional MUC1 Variants on Cardiometabolic, Renal, and Hematological Traits in the Taiwanese Population. Int J Mol Sci. 2021 Sep 30;22(19):10641.
  14. Kuan-Hung Yeh, Yao-Ting Chang, Jyh-Ming Jimmy Juang, Fu-Tien Chiang, Ming-Sheng Teng, Semon Wu, Jeng-Feng Lin, Yu-Lin Ko. Combined corrected QT interval and growth differentiation factor-15 level has synergistic predictive value for long-term outcome of angiographically confirmed coronary artery disease. Int J Clin Pract. 2021 Jul;75(7):e14180.
  15. Hsu LA, Chou HH, Teng MS, Wu S, Ko YL*. Circulating chemerin levels are determined through circulating platelet counts in nondiabetic Taiwanese people: A bidirectional Mendelian randomization study. Atherosclerosis. Atherosclerosis. 2021 Mar;320:61-69.
  16. Hsin-Hua Chou, Ming-Sheng Teng, Lung-An Hsu, Leay-Kiaw Er, Semon Wu, Yu-Lin Ko. Circulating chemerin level is associated with metabolic, biochemical and haematological parameters-A population-based study. Clin Endocrinol (Oxf). 2021 Jun;94(6):927-939.
  17. Duan DM, Jhang JY, Wu S, Teng MS, Hsu LA, Ko YL*. Modification effect of sex and obesity on the correlation of LEP polymorphisms with leptin levels in Taiwanese obese women. Mol Genet Genomic Med. 2020 Mar;8(3):e1113.
  1. 心血管研究團隊，成員:葉冠宏醫師、周星輝醫師、林正豐醫師、段德敏醫師等。
  2. 新陳代謝科醫師團隊，成員:余麗嬌醫師、廖瑜皇醫師。
  3. 神經外科研究團隊，成員:徐賢達醫師。