Exploration of Interethnic Variation in the Ibuprofen Metabolizing Enzyme CYP2C9: A Cautionary Guide for Treatment of COVID-19 Symptoms

Abstract

Background Coronavirus disease 2019 (COVID-19), is a rapidly spreading infectious illness that causes a debilitating respiratory syndrome. While non-steroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, may be prescribed for the management of pain and fever, controversy arose on the use of ibuprofen due to the possibility of a worse COVID-19 prognosis. P450 enzyme CYP2C9 are known to be involved in the metabolism of NSAIDs. Although no direct evidence of pharmacogenomics data in patients with COVID-19 was available at the time of writing this manuscript, there are plausible mechanisms by which genetic determinants may play a role in adverse drug responses (ADRs). Methods In this work, several genetic markers were analyzed across diverse ethnic backgrounds to identify population differences in drug responses and toxicity events associated with ibuprofen treatment. A cohort of 101 Jordanian Arab samples were retrospectively recruited and genotyped using Affymetrix DMET Plus Premier Package, within the context of over 100,000 global subjects in 417 published reports. Results Genetic structure analysis across populations validated that Jordanian Arabs share the closest CYP2C9 sequence homology to Near East and European populations. The Jordanian Arab population was also shown to be genetically heterogeneous for CYP2C9. However, European populations are 7.2x more likely to show impaired ibuprofen metabolism than Sub-Saharan populations, and 4.5x more likely than East Asian ancestry populations. Conclusions These findings are supported by recent European reports of potential harm with ibuprofen usage in patients with COVID-19 symptoms. Hence, the use of modern genomic tools coupled with a proactive assessment of the most likely gene-drug candidates will lead to a better understanding of the role of pharmacogenetics for COVID-19 and more effective treatments.