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

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Abstract

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.

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Funding

This study was supported by the Fundamental Research Grant Scheme by the Ministry of Higher Education, Malaysia (FRGS/1/2020/SKK01/UPM/02/1).

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Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia

    Njundu Jatta, Johnson Stanslas, Wen Chung Ho, Wan Ahmad Kammal Wan Syazween Lyana & Kang Nien How

  2. School of Pharmacy, MAHSA University, Bandar Saujana Putra, Jenjarom, Selangor, Malaysia

    Audrey Chee Hui Yong

  3. Dermatology Unit, Hospital Sultan Abdul Aziz Shah, Universiti Putra Malaysia, Serdang, Malaysia

    Wen Chung Ho, Wan Ahmad Kammal Wan Syazween Lyana & Kang Nien How

  4. Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia

    Eng Wee Chua

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  1. Njundu Jatta
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KNH and NJ decided on the topic, NJ did the literature search, and JS, ACHY, WCH, WSLWAK, and EWC contributed to reviewing and finalizing the manuscript. All the authors have read and approved the final version of the manuscript.

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Correspondence to Kang Nien How.

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Jatta, N., Stanslas, J., Yong, A.C.H. et al. Whole blood hydroxychloroquine: Does genetic polymorphism of cytochrome P450 enzymes have a role?. Clin Exp Med 23, 4141–4152 (2023). https://doi.org/10.1007/s10238-023-01142-w

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