Pharmacogenetics of Methotrexate in Rheumatoid Arthritis

甲氨蝶呤治疗类风湿性关节炎的药物遗传学

• 批准号: 7454971
• 负责人: LAURA B HUGHES
• 金额: $ 11.45万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7454971
• 关键词: AMP Deaminase; Adenosine; Adenosine Monophosphate; Adverse effects; African American; Alabama; Alleles; Award; Biometry; Caucasians; Caucasoid Race; Characteristics; Clinical; Clinical Data; Clinical Immunology; Clinical Investigator; Clinical Trials; Code; Complementary DNA; DNA; Data; Databases; Deaminase; Development; Disease; Doctor of Philosophy; Dose; Drug toxicity; Effectiveness; Enzymes; Ethnic Origin; Event; Fellowship; Folate; Folic Acid; Follow-Up Studies; Foundations; Frequencies; Funding; Gene Frequency; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Haplotypes; Human; Human Genetics; Individual; Inflammatory; Knowledge; Manuscripts; Medicine; Mentors; Mentorship; Methotrexate; Minor; Mutation; Numbers; Observational Study; Outcome; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Pharmacogenetics; Phase; Play; Population; Predisposition; Preparation; Protein Isoforms; Public Domains; Race; Recruitment Activity; Research; Research Personnel; Rheumatoid Arthritis; Rheumatology; Role; Scanning; Single Nucleotide Polymorphism; Statistical Methods; Testing; Toxic effect; Treatment outcome; Universities; Work; adenosine deaminase; career; cohort; extracellular; innovation; interest; novel; patient oriented research; posters; professor; programs; prospective; response; skills; trait

DESCRIPTION (provided by applicant): Laura B. Hughes, MD, MSPH has a background in rheumatology and has research skills in human genetics and biostatistics. She completed her rheumatology fellowship at the University of Alabama at Birmingham (UAB) and is a newly appointed Assistant Professor of Medicine in the Division of Clinical Immunology and Rheumatology. During her fellowship Dr. Hughes became interested in the role of genetics in susceptibility and outcomes in rheumatoid arthritis (RA). Under the mentorship of S. Louis Bridges, Jr., MD, PhD she received a Clinical Investigator Fellowship Award from the UAB GCRC and was the recipient of the UAB Walter B. Frommeyer, Jr. Fellowship in Investigative Medicine. As a fellow, Dr. Hughes focused her research on her mentor's NIH-funded project entitled, "Pharmacogenetic Markers of Methotrexate (MTX) in RA". She has presented results from this research in poster form and has 2 manuscripts in preparation. Dr. Hughes' career goals are to become a leader in research that identifies genetic predictors of drug response and toxicity in patients with RA and how these markers may vary according to race/ethnicity. Dr. Hughes has been fortunate to work with strong investigators in clinical trials, pharmacogenetic research, and statistical genetics who have given their commitment to assist in her career development. This proposal entails an educational plan that will increase her knowledge of human genetics and pharmacogenetics, as well as the technical and statistical methods required to conduct high quality patient-oriented research. The scientific project expands the scope of her previous work on genetic markers of response and toxicty to MTX by analyzing functional polymorphisms in genes encoding 2 key enzymes inhibited by MTX therapy; adenosine monophosphate deaminase-1 (AMPD1) and adenosine deaminase-1 (ADA1), in Caucasians and African-Americans with RA. This proposal will provide Dr. Hughes the necessary skills to perform high quality, innovative pharmacogenetic research that will directly impact the clinical care of patients with RA.

描述(由申请人提供)： Laura B.Hughes，医学博士，MSPH拥有风湿学背景，并在人类遗传学和生物统计学方面拥有研究技能。她在阿拉巴马大学伯明翰分校(UAB)完成了风湿学奖学金，是临床免疫学和风湿病学系新任命的医学助理教授。在她担任研究员期间，休斯博士对遗传学在类风湿性关节炎(RA)的易感性和预后中的作用产生了兴趣。在S.Louis Bridges，Jr.，医学博士和博士的指导下，她获得了UAB GCRC的临床研究人员奖学金奖，并获得了UAB Walter B.Frommeyer，Jr。研究医学奖学金。作为一名研究员，休斯博士将她的研究重点放在了她的导师的NIH资助的项目上，该项目名为“甲氨蝶呤(MTX)在类风湿关节炎中的药物遗传标记”。她以海报的形式展示了这项研究的结果，并准备了两份手稿。休斯博士的职业目标是成为研究领域的领导者，该研究确定类风湿关节炎患者药物反应和毒性的遗传预测因素，以及这些标记如何随种族/民族而变化。休斯博士有幸在临床试验、药物遗传学研究和统计遗传学领域与强大的研究人员合作，他们致力于帮助她的职业发展。这项建议需要一个教育计划，以增加她对人类遗传学和药物遗传学的知识，以及进行高质量面向患者的研究所需的技术和统计方法。该科学项目扩大了她之前在MTX反应和毒性遗传标记方面的工作范围，方法是分析编码两种关键酶的基因的功能多态性，这两种酶是在患有RA的高加索人和非裔美国人中，编码被MTX治疗抑制的腺苷一磷酸脱氨酶-1(AMPD1)和腺苷脱氨酶-1(ADA1)。这项建议将为休斯博士提供必要的技能，以进行高质量的创新药物遗传学研究，这些研究将直接影响RA患者的临床护理。