Neurology. 2010 Jan 5;74 Suppl 1:S62-9. doi: 10.1212/WNL.0b013e3181c980fb.
Genetic polymorphisms and variable expression of drug receptors, metabolizing enzymes, and transporters have been linked to interindividual differences in efficacy and toxicity of many Food and Drug Administration-approved therapeutic agents. In multiple sclerosis, the combination of heterogeneity of disease pathology and significant variation in clinical response to disease-modifying agents necessitates the definition of biomarkers that can a priori predict therapeutic response and define appropriate therapeutic regimens. Pharmacogenomic studies will directly address the question of heterogeneity by analysis of the correlation between different genomic variants and clinical responses to therapy. These studies will include longitudinal designs, maximize clinical response variables, include whole-genome technologies, use large patient cohorts, and require the development of novel mathematical algorithms designed to integrate the wealth of disparate data to identify modest genetic effects and interactions.
遗传多态性和药物受体、代谢酶和转运体的可变表达与许多经美国食品和药物管理局批准的治疗药物的疗效和毒性的个体差异有关。在多发性硬化症中，疾病病理学的异质性和对疾病修饰剂的临床反应的显著变化相结合，需要定义能够预先预测治疗反应并确定适当治疗方案的生物标志物。通过分析不同基因组变异与治疗反应之间的相关性，药物基因组学研究将直接解决异质性问题。这些研究将包括纵向设计，最大限度地提高临床反应变量，包括全基因组技术，使用大型患者队列，并需要开发新的数学算法，旨在整合大量不同的数据，以识别适度的遗传效应和相互作用。
