Ethnic variation in risk genotypes based on single nucleotide polymorphisms (SNPs) of the interferon-inducible transmemb
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ORIGINAL ARTICLE
Ethnic variation in risk genotypes based on single nucleotide polymorphisms (SNPs) of the interferon‑inducible transmembrane 3 (IFITM3) gene, a susceptibility factor for pandemic 2009 H1N1 influenza A virus Yong‑Chan Kim1,2 · Byung‑Hoon Jeong1,2 Received: 19 September 2020 / Accepted: 3 November 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The interferon-inducible transmembrane 3 (IFITM3) protein is an effector of the host innate immune system that shows defensive activity against a wide range of viruses, including the influenza A virus. Previous studies have reported that three transcription-related regulatory single nucleotide polymorphisms (SNPs), rs12252, rs34481144, and rs6598045, showed potent associations with the severity of pandemic influenza A 2009 infection and susceptibility to this virus, respectively. However, the distribution of the risk genotypes of these three SNPs according to ethnic background has remained elusive. In this study, we compared the genotype and allele frequencies of the IFITM3 polymorphisms among several ethnic groups including American, African, European, South Asian, and East Asian using chi-square test. In addition, we analyzed the worldwide distribution of risk genotypes for pandemic influenza A 2009 virus infection. We found that the genotype and allele distributions of the rs12252, rs34481144, and rs6598045 SNPs were significantly different among several ethnic groups. In addition, the risk genotypes of the IFITM3 polymorphisms were also significantly different worldwide. To the best of our knowledge, this was the first simultaneous estimation of the risk genotypes of the IFITM3 gene with respect to pandemic influenza A 2009 virus infection. Keywords IFITM3 · Interferon · SNP · rs12252 · rs34481144 · rs6598045 · Promoter region, pandemic influenza A 2009
Introduction The interferon-inducible transmembrane 3 (IFITM3) protein is a potent antiviral effector encoded by the IFITM3 gene, which is classified as a small interferon-stimulated gene (Diamond and Farzan 2013; Feeley et al. 2011; Kim and Jeong 2017; Shi et al 2017; Zani and Yount 2018). The IFITM3 protein protects hosts from viral invasion by prohibiting hemifusion between host cells and various viruses, including the influenza A virus (Bailey et al. 2014; Brass et al. 2009; Li et al. 2013). The length of the human IFITM3 * Byung‑Hoon Jeong [email protected] 1
Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Republic of Korea
Department of Bioactive Material Sciences and Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, Jeonbuk 54896, Republic of Korea
2
protein is relatively short (133 aa), and the IFITM3 protein contains an interspecific well-conserved CD225 domain (John et al. 2013). A previous study reported that ablation of the IFITM3 gene results in severe pneumonia in mildly influenza-infected mice and that elevated expression of the IFITM3 protein provides a dramatic increase in the s
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