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: 6861243
• 负责人: LAURA B HUGHES
• 金额: $ 10.7万
• 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/6861243
• 关键词: adenosine deaminase; adenosine monophosphate; clinical research; genetic markers; human subject; methotrexate; patient oriented research; pharmacogenetics; rheumatoid arthritis; single nucleotide polymorphism

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）： 劳拉B。休斯，医学博士，MSPH有风湿病学的背景，并在人类遗传学和生物统计学的研究技能。她在伯明翰的亚拉巴马大学（UAB）完成了她的风湿病学奖学金，是临床免疫学和风湿病学系新任命的医学助理教授。在她的研究期间，Hughes博士对遗传学在类风湿性关节炎（RA）易感性和结局中的作用产生了兴趣。在S.小路易斯·布里奇斯她获得了UAB GCRC的临床研究者奖学金，并获得了UAB Walter B。小弗罗迈尔研究医学奖学金。作为一名研究员，休斯博士将她的研究集中在她导师的NIH资助的项目上，该项目名为“RA中甲氨蝶呤（MTX）的药物遗传学标记”。她以海报的形式展示了这项研究的结果，并准备了2份手稿。休斯博士的职业目标是成为研究的领导者，确定RA患者药物反应和毒性的遗传预测因子，以及这些标记物如何根据种族/民族而变化。Hughes博士有幸与临床试验，药物遗传学研究和统计遗传学方面的强大研究人员合作，他们致力于协助她的职业发展。这项建议需要一个教育计划，将增加她的人类遗传学和遗传药理学的知识，以及进行高质量的以病人为导向的研究所需的技术和统计方法。该科学项目通过分析编码MTX治疗抑制的2种关键酶的基因的功能多态性，扩大了她以前对MTX的反应和毒性的遗传标记的工作范围;在白人和非洲裔美国人中，腺苷单磷酸脱氨酶-1（AMPD 1）和腺苷脱氨酶-1（ADA 1）患有RA。该提案将为Hughes博士提供必要的技能，以进行高质量，创新的药物遗传学研究，这将直接影响RA患者的临床护理。