Whole blood hydroxychloroquine: Does genetic polymorphism of cytochrome P450 enzymes have a role?

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.

Keywords: Antimalarial; Genetic polymorphism; Hydroxychloroquine; Lupus; Pharmacogenomic.

Publication types

  • Review

MeSH terms

  • Antirheumatic Agents* / therapeutic use
  • Cytochrome P-450 Enzyme System / therapeutic use
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Lupus Erythematosus, Systemic* / drug therapy
  • Lupus Erythematosus, Systemic* / genetics
  • Lupus Nephritis* / complications
  • Polymorphism, Genetic
  • Quality of Life


  • Hydroxychloroquine
  • Antirheumatic Agents
  • Cytochrome P-450 Enzyme System