药物基因组学
药物遗传学
单核苷酸多态性
医学
甲氨蝶呤
亚甲基四氢叶酸还原酶
药理学
生物信息学
SNP公司
个性化医疗
药物治疗
精密医学
药物开发
疾病
药品
计算生物学
功效
重症监护医学
临床试验
药物反应
基因
生物
内科学
遗传学
基因型
作者
Mengda Cao,Miao Guo,Deqin Wu,Ling Meng
出处
期刊:Current Drug Metabolism
[Bentham Science]
日期:2018-12-27
卷期号:19 (14): 1182-1187
被引量:15
标识
DOI:10.2174/1389200219666171227201047
摘要
Background: Methotrexate (MTX) is a folate analogue with high therapeutic efficiency in the treatment of cancers and autoimmune diseases. The efficacy and toxicity of MTX may be altered by genetic polymorphisms in genes involved in MTX metabolic pathway. Personalized pharmacotherapy based on gene polymorphisms enables a more efficient, compatible and cost-effective treatment of patients. Objective: The present article aims to review genetic polymorphisms associated with MTX pharmacokinetics, toxicity, and outcome, and points out future development directions of individualized MTX therapy. Methods: Details regarding the pharmacogenetics and pharmacogenomics of MTX are obtained from PubMed literatures. Conclusion: The influences of single nucleotide polymorphisms (SNPs) in genes involved in MTX pathway are controversial. Many pharmacogenetic associations are disease specific and race specific. Present studies have almost limited to some certain ethnic groups and diseases. The data from these studies are not convincing enough to draw far-reaching conclusions about the applicability of MTX pharmacogenetics in clinical practice. Studies with large scale and multiple centers are needed in the future. MTX-PG inhibits folic metabolism through three mechanisms. TS, MTHFR and ATIC are the rate-limiting enzymes separately. The function of SNPs in these genes is often onesided. Works focusing on the analysis of polymorphism in MTX transporters should be more efficient and meaningful. Keywords: MTX, SNP, efficacy, toxicity, pharmacogenomics, polymorphisms.
科研通智能强力驱动
Strongly Powered by AbleSci AI