ArticleBMC medical genomics2022
Relationship of cytochrome P450 gene polymorphisms with blood concentrations of hydroxychloroquine and its metabolites and adverse drug reactions.
Article in BMC medical genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
- The DHCQ/HCQ metabolic ratio and CYP2C8 Genotype are associated with lipid profile improvement in systemic lupus erythematosus patients treated with hydroxychloroquine.Arthritis research & therapy · 2026Article
- Refining lupus management: a comprehensive review of HCQ blood levels.Rheumatology advances in practice · 2025Review
- Early-onset bull's eye maculopathy due to hydroxychloroquine in rheumatoid arthritis and myasthenia gravis.International journal of ophthalmology · 2025Article
- Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes.JAMA network open · 2024Article
- Genetic variation of CYP2C9 gene and its correlation with cardiovascular disease risk factors.Molecular biology reports · 2024Article
- Therapeutic Drug Monitoring in Patients with Systemic Lupus Erythematosus: Utility and Gaps.Journal of clinical medicine · 2024Review
- Genotype-guided new approach for dose optimisation of hydroxychloroquine administration in Chinese patients with SLE.Lupus science & medicine · 2023Article
- Gut microbiota and host cytochrome P450 characteristics in the pseudo germ-free model: co-contributors to a diverse metabolic landscape.Gut pathogens · 2023Article
- Pharmacogenetics to optimize immunosuppressant therapy in systemic lupus erythematosus: a scoping review.PharmacogenomicsArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHydroxychloroquine (HCQ) is a cornerstone therapy for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study aimed to investigate the relationship of cytochrome P450 (CYP450) gene polymorphisms with blood concentrations of HCQ and its metabolites and adverse drug reactions (ADRs) in patients with SLE and RA.
methodsA cohort of 146 patients with SLE and RA treated with HCQ was reviewed. The ADRs of the patients were recorded. The blood concentrations of HCQ and its metabolites were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Genotyping of single nucleotide polymorphisms (SNPs) in CYP450, a metabolic enzyme involved in the HCQ metabolic pathway, was performed using a MassARRAY system. The chi-square test, T-test, and one-way analysis of variance were used to analyse data.
resultsAmong 29 candidate SNPs, we found that CYP3A4 (rs3735451) was significantly associated with blood levels of HCQ and its metabolites in both the unadjusted model and adjusted model (patients taking HCQ for > 10 years) (P < 0.05). For CYP3A5 (rs776746), a greater risk of skin and mucous membrane ADRs was associated with the TT genotype than with the CT + CC genotypes (P = 0.033). For CYP2C8 (rs1058932), the AG genotype carried a greater risk of abnormal renal function than the AA + GG genotype (P = 0.017); for rs10882526, the GG genotype carried a greater risk of ophthalmic ADRs than the AA + AG genotypes (P = 0.026).
conclusionsThe CYP2C8 (rs1058932 and rs10882526) and CYP3A5 (rs776746) polymorphisms are likely involved in the ADRs of HCQ. Gene polymorphism analysis of CYP450 and therapeutic drug monitoring of HCQ and its metabolites might be useful to optimise HCQ administration and predict ADRs.
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