背景:药物遗传学评估遗传变异如何影响药物反应。如今,基因测试取得了进展,变得更加实惠,其整合得到了更强有力的临床证据的支持。诸如CPIC(临床药物遗传学实施联盟)和诸如PharmGKB之类的资源之类的指南促进了基于基因型的处方;FDA等组织在开始某些药物之前促进了基因测试。预防性药物遗传学小组似乎很有希望,但需要对生物标志物和不同人群进行进一步研究。这篇综述的目的是分析基因型-药物反应关系的最新证据,以检查患者的遗传特征如何影响对治疗的临床反应。并分析需要进一步研究的研究领域,以推进基于基因的精准医学。
方法:在PubMed上进行了系统搜索,以确定研究基因型-药物反应关系的文章。搜索策略包括“药物遗传学”等术语,“个性化治疗”,“精准医学”,“剂量调整”,“个性化剂量”,“临床常规”,和“临床实践”。“临床试验,观察性研究,纳入了2013年至2023年间以英语或西班牙语发表的荟萃分析。最初的搜索结果共有136篇文章用于分析。
结果:49篇文章被纳入2名研究者审查后的最终分析。发现了阿片类药物等药物的遗传多态性与药物反应或毒性之间的关系,GLP-1激动剂,他克莫司,口服抗凝剂,抗肿瘤塑料,非典型抗精神病药,efavirenz,氯吡格雷,拉莫三嗪,抗TNFα药物,伏立康唑,抗抑郁药,或他汀类药物。然而,对于像二甲双胍这样的药物,喹硫平,伊立替康,比索洛尔,和抗VEGF药物,在基因型和应答之间没有发现统计学上显著的关联.
结论:这篇综述中分析的研究表明,遗传变异与个体药物反应之间存在很强的相关性,支持使用药物遗传学进行治疗优化。然而,对于某些药物,如二甲双胍或喹硫平,基因型对其反应的影响尚不清楚.更多样本量更大的研究,更大的种族多样性,需要考虑非遗传因素。分析方法缺乏标准化和基因检测的可及性是该领域的重大挑战。作为结论,药物遗传学在个性化医学中显示出巨大的潜力,但需要进一步的研究。
BACKGROUND: Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Pharmacogenetics Implementation Consortium) and resources like PharmGKB facilitate genotype-based prescribing; and organizations like the FDA promote genetic testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers and diverse populations is needed. The aim of this review is to analyze recent evidence on the genotype-drug response relationship to examine how the genetic profile of patients influences the clinical response to treatments, and analyze the areas of research that need further study to advance towards a genetic-based precision medicine.
METHODS: A systematic search was conducted on PubMed to identify articles investigating the genotype-drug response relationship. The search strategy included terms such as \"pharmacogenetics\", \"personalized treatment\", \"precision medicine\", \"dose adjustment\", \"individualizing dosing\", \"clinical routine\", and \"clinical practice.\" Clinical trials, observational studies, and meta-analyses published in English or Spanish between 2013 and 2023 were included. The initial search resulted in a total of 136 articles for analysis.
RESULTS: 49 articles were included for the final analysis following review by 2 investigators. A relationship between genetic polymorphisms and drug response or toxicity was found for drugs such as opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNFα agents, voriconazole, antidepressants, or statins. However, for drugs like metformin, quetiapine, irinotecan, bisoprolol, and anti-VEGF agents, no statistically significant association between genotype and response was found.
CONCLUSIONS: The studies analyzed in this review suggest a strong correlation between genetic variability and individual drug responses, supporting the use of pharmacogenetics for treatment optimization. However, for certain drugs like metformin or quetiapine, the influence of genotype on their response remains unclear. More studies with larger sample sizes, greater ethnic diversity, and consideration of non-genetic factors are needed. The lack of standardization in analysis methods and accessibility to genetic testing are significant challenges in this field. As a conclusion, pharmacogenetics shows immense potential in personalized medicine, but further research is required.