Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan.
Mol Diagn Ther. 2012 Feb 1;16(1):15-27. doi: 10.1007/BF03256426.
In pharmacogenomics studies, gene-gene interactions play an important role in characterizing a trait that involves complex pharmacokinetic and pharmacodynamic mechanisms, particularly when each involved feature only demonstrates a minor effect. In addition to the candidate gene approach, genome-wide association studies (GWAS) are widely utilized to identify common variants that are associated with treatment response. In the wake of recent advances in scientific research, a paradigm shift from GWAS to whole-genome sequencing is expected, because of the reduced cost and the increased throughput of next-generation sequencing technologies. This review first outlines several promising methods for addressing gene-gene interactions in pharmacogenomics studies. We then summarize some candidate gene studies for various treatments with consideration of gene-gene interactions. Furthermore, we give a brief overview for the pharmacogenomics studies with the GWAS approach and describe the limitations of these GWAS in terms of gene-gene interactions. Future research in translational medicine promises to lead to mechanistic findings related to drug responsiveness in light of complex gene-gene interactions and will probably make major contributions to individualized medicine and therapeutic decision-making.
在药物基因组学研究中，基因-基因相互作用在描述涉及复杂药代动力学和药效动力学机制的特征方面起着重要作用，特别是当每个相关特征仅表现出较小的影响时。除了候选基因方法外，全基因组关联研究（GWAS）也被广泛用于识别与治疗反应相关的常见变体。随着科学研究的最新进展，预计会从 GWAS 向全基因组测序转变，这是由于下一代测序技术的成本降低和通量增加。这篇综述首先概述了几种有前途的方法，用于解决药物基因组学研究中的基因-基因相互作用。然后，我们总结了一些候选基因研究，考虑了基因-基因相互作用的各种治疗方法。此外，我们还简要概述了采用 GWAS 方法的药物基因组学研究，并描述了这些 GWAS 在基因-基因相互作用方面的局限性。转化医学的未来研究有望根据复杂的基因-基因相互作用得出与药物反应性相关的机制发现，并可能为个体化医学和治疗决策做出重大贡献。
