Effects of Genetic Polymorphisms of CYP450 Enzymes on Blood Hydroxychloroquine Levels and Clinical Response Among Patients With Cutaneous Lupus Erythematosus

Abstract

Whole blood hydroxychloroquine (WBHCQ) levels were found to correlate with cutaneous lupus (CLE) disease severity. Studies have shown HCQ to be highly variable in blood concentrations and clinical response among patients; however, the exact cause of this variation is not well understood. Genetic polymorphism of CYP450 enzymes was suspected to be a possible contributing factor. This study aimed to determine the effects of genetic polymorphism of CYP450 enzymes on clinical response to HCQ among Malaysians with CLE and its association with blood [HCQ], [DHCQ] or [HCQ]: [DHCQ] ratio. This study was a multicentre cohort study targeting CLE subjects on HCQ, recruited from five main hospitals in Malaysia. A total of 33 subjects were recruited from 1 September 2021 to 30 November 2023. Blood [HCQ], [DHCQ] or its concentration ratio and clinical response to HCQ were the outcome variables determined. Statistical Analysis showed that CYP2D6*10 was significantly associated with blood [HCQ] (p < 0.05), while CYP3A5*3 was shown to be significantly associated with [DHCQ]: [HCQ] ratio (p < 0.05). However, a statistically significant association was not observed between identified SNPs and clinical response to HCQ (OR: 4.444, CI: 0.770, 25.654, p = 0.095). These findings are aligned with those reported previously on blood HCQ and CYP polymorphism; however, clinical response to HCQ and CYP polymorphism is still debatable, as we did not observe any significant association. CYP450 genetic polymorphism significantly affects levels of HCQ in patients. Thus, individual genotypes of CYP450 enzymes may be considered for the optimum use of HCQ among CLE subjects.