Zampatti Stefania, Peconi Cristina, Farro Juliette, Piras Fabrizio, Pellicano Clelia, Caltagirone Carlo, Giardina Emiliano
Genomic Medicine Laboratory UILDM, IRCCS Santa Lucia Foundation, Rome, Italy.
Neuropsychiatry Laboratory, Department of Clinical Neuroscience and Neurorehabilitation, IRCCS Santa Lucia Foundation, Rome, Italy.
Front Pharmacol. 2025 Jul 21;16:1627239. doi: 10.3389/fphar.2025.1627239. eCollection 2025.
The integration of pharmacogenetics into personalized medicine enables the optimization of drug selection and dosage, maximizing therapeutic benefits while minimizing the risk of adverse drug reactions. The association between alleles and ARIA, a known adverse reaction in Alzheimer's disease patients treated with anti-amyloid monoclonal antibodies, has led to the inclusion of genotyping among conventional pharmacogenetic tests. Given the dual role of alleles, the widespread implementation of this genetic test requires caution and should be accompanied by appropriate genetic counselling. genotyping is uniquely positioned at the intersection of pharmacogenetics and germline testing: it provides insight not only into drug safety (specifically the risk of Amyloid-Related Imaging Abnormalities) but also into familial risk for developing Alzheimer's disease. Carriers of risk alleles, especially homozygotes, face the highest risk and require close monitoring. While genotyping can inform treatment decisions, it also raises ethical concerns due to the broader implications of disclosing genetic risk information for neurodegenerative diseases. Identifying a high-risk genotype in a patient substantially impacts family members. Therefore, patients considered for treatment with anti-amyloid monoclonal antibodies should receive comprehensive pre- and post-test genetic counseling that goes beyond traditional standards, as currently provided for other peculiar tests. Such counseling ensures that patients are adequately informed about potential outcomes, psychological impacts, and familial implications. It also supports ethical decision-making and facilitates truly informed consent, helping to prevent deterministic or overly simplistic interpretations of genetic risk.
将药物遗传学整合到个性化医疗中，能够优化药物选择和剂量，在将药物不良反应风险降至最低的同时，使治疗效益最大化。等位基因与ARIA（接受抗淀粉样蛋白单克隆抗体治疗的阿尔茨海默病患者中一种已知的不良反应）之间的关联，已导致在传统药物遗传学检测中纳入基因分型。鉴于等位基因的双重作用，广泛开展这种基因检测需要谨慎，并应辅以适当的遗传咨询。基因分型独特地处于药物遗传学和种系检测的交叉点：它不仅能洞察药物安全性（特别是淀粉样蛋白相关影像学异常的风险），还能洞察患阿尔茨海默病的家族风险。风险等位基因的携带者，尤其是纯合子，面临的风险最高，需要密切监测。虽然基因分型可为治疗决策提供信息，但由于披露神经退行性疾病遗传风险信息会产生更广泛的影响，它也引发了伦理问题。在患者中识别出高风险基因型会对其家庭成员产生重大影响。因此，考虑接受抗淀粉样蛋白单克隆抗体治疗的患者应接受超越传统标准的全面的检测前和检测后遗传咨询，就像目前为其他特殊检测所提供的那样。这种咨询可确保患者充分了解潜在结果、心理影响和家族影响。它还支持伦理决策并促进真正的知情同意，有助于防止对遗传风险的确定性或过于简单化的解读。
