Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Frequency of Combined IFITM3 Haplotype Involving the Reference Alleles of Both rs12252 and rs34481144 is in Line with COVID-19 Standardized Mortality Ratio of Ethnic Groups in England

Version 1 : Received: 15 May 2020 / Approved: 16 May 2020 / Online: 16 May 2020 (17:38:28 CEST)
Version 2 : Received: 14 August 2020 / Approved: 20 August 2020 / Online: 20 August 2020 (04:29:43 CEST)

A peer-reviewed article of this Preprint also exists.

Journal reference: PeerJ 2020
DOI: 10.7717/peerj.10402


Evidence was recently brought forward in England and the USA that Black, Asian, Latinos and Minority Ethnic people present higher mortality risk from COVID-19 than White people. While socioeconomic factors were suggested to contribute to this trend, they arguably do not explain the range of the differences observed, allowing for possible genetic implications. Almost concurrently, the analysis of a cohort in Chinese COVID-19 patients proposed an association between the severity of the disease and the presence of the minor allele of rs12252 of the IFITM3 gene. This SNP, together with rs34481144, are the two most studied polymorphisms of IFITM3 and have been associated in the past with increased severity in Influenza, Dengue, Ebola, and HIV viruses. Interferon-induced transmembrane protein 3 is an immune effector protein that is pivotal for the restriction of viral replication, but also for the regulation of cytokine production. Following up to these two developments in the SARS-CoV-2 pandemic, the present study investigates a possible connection between differences in mortality of ethnic groups in England and the haplotypes of rs12252 and rs34481144. The respective allele frequencies were collected for all 1000 Genomes Project’s populations and subgroups were pooled wherever possible to create correspondences with ethnic groups in England. A strong correlation was observed between the reported Standardized Mortality Ratios and the frequency of the combined haplotype of both reference alleles. If confirmed clinically, this finding could be pointing at possible hijacking of IFITM3 by SARS-CoV-2 virus and is expected to impact our understanding of the disease mechanisms behind COVID-19.

Subject Areas

COVID-19; SARS-CoV-2; pandemic; IFITM3; rs12252; rs34481144; ethnic groups; bame; cytokine storm

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