Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
School of Pharmacy, MAHSA University, Bandar Saujana Putra, Jenjarom, Selangor, Malaysia.
Clin Exp Med. 2023 Dec;23(8):4141-4152. doi: 10.1007/s10238-023-01142-w. Epub 2023 Jul 22.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and multifactorial etiologies ranging from environmental to genetic. SLE is associated with dysregulated immunological reactions, with increased immune complex formation leading to end-organ damages such as lupus nephritis, cutaneous lupus, and musculoskeletal disorders. Lupus treatment aims to reduce disease activity, prevent organ damage, and improve long-term patient survival and quality of life. Antimalarial, hydroxychloroquine (HCQ) is used as a first-line systemic treatment for lupus. It has shown profound efficacy in lupus and its associated conditions. However, wide variation in terms of clinical response to this drug has been observed among this group of patients. This variability has limited the potential of HCQ to achieve absolute clinical benefits. Several factors, including genetic polymorphisms of cytochrome P450 enzymes, have been stipulated as key entities leading to this inter-individual variation. Thus, there is a need for more studies to understand the role of genetic polymorphisms in CYP450 enzymes in the clinical response to HCQ. Focusing on the role of genetic polymorphism on whole blood HCQ in lupus disorder, this review aims to highlight up-to-date pathophysiology of SLE, the mechanism of action of HCQ, and finally the role of genetic polymorphism of CYP450 enzymes on whole blood HCQ level as well as clinical response in lupus.
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，临床表现广泛，病因包括环境和遗传等多种因素。SLE 与免疫反应失调有关，免疫复合物的形成增加会导致肾脏、皮肤和肌肉骨骼等器官受损。狼疮的治疗目的是减轻疾病活动度、预防器官损伤，以及提高患者的长期生存率和生活质量。抗疟药羟氯喹（HCQ）是治疗狼疮的一线药物。它在狼疮及其相关疾病中具有显著的疗效。然而，在这组患者中，观察到对该药物的临床反应存在广泛的差异。这种变异性限制了 HCQ 实现绝对临床获益的潜力。多种因素，包括细胞色素 P450 酶的遗传多态性，被认为是导致这种个体间差异的关键因素。因此，需要更多的研究来了解细胞色素 P450 酶的遗传多态性在 HCQ 临床反应中的作用。本综述聚焦于遗传多态性对狼疮患者全血 HCQ 的作用，旨在强调 SLE 的最新病理生理学、HCQ 的作用机制，以及细胞色素 P450 酶的遗传多态性对全血 HCQ 水平和狼疮临床反应的作用。
