Exploration of interethnic variation in the ibuprofen metabolizing enzyme CYP2C9: a cautionary guide for treatment of COVID-19 symptoms

Almarzooq, A. A.

Coronavirus disease 2019 (COVID-19), is a rapidly spreading infectious illness that causes a debilitating respiratory syndrome. Supportive therapy remains the standard for mild-to-moderate cases, including treatment with non-steroidal anti-inflammatory drugs (NSAIDs) e.g. ibuprofen, however such medications may increase COVID-19 complications when used in patients with acute viral respiratory infections. P450 enzyme CYP2C9 are known to be involved in the metabolism of NSAIDs, however, their pharmacogenetic data are limited. This study aims to better understand the genetic landscape of CYP2C9 sequence variation across different ethnic and geographic groups, in correlation with ibuprofen dosing guidelines. A cohort of 101 Jordanian Arab samples were retrospectively recruited and genotyped using Affymetrix DMET Plus Premier Package. This study identified 18 single nucleotide polymorphisms (SNPs) within CYP2C9 in these Jordanian Arabs, within the context of over 100,000 global subjects in 417 published reports. Genetic structure analysis across populations revealed that Jordanian Arabs share the closest CYP2C9 sequence homology to Near East and European populations. 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.. This is the most comprehensive and up-to-date analysis for CYP2C9 allele frequencies across multi-ethnic populations world-wide. 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.