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首页> 外文期刊>Journal of genetics >Assessment of risk conferred by coding and regulatory variations of TMPRSS2 and CD26 in susceptibility to SARS-CoV-2 infection in human
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Assessment of risk conferred by coding and regulatory variations of TMPRSS2 and CD26 in susceptibility to SARS-CoV-2 infection in human

机译：TMPRSS2和CD26在人类SARS-COV-2感染的易感性中赋予风险的评估

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At present, more than 200 countries and territories are directly affected by the coronavirus disease-19 (COVID-19) pandemic. Incidence and case fatality rate are significantly higher among elderly individuals (age60 years), type 2 diabetes and hypertension patients. Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection. We hypothesised that common variants from TMPRSS2 and CD26 may play critical role in infection susceptibility of predisposed population or group of individuals. Coding (missense) and regulatory variants from TMPRSS2 and CD26 were studied across 26 global populations. Two missense and five regulatory SNPs were identified to have differential allelic frequency. Significant linkage disequilibrium (LD) signature was observed in different populations. Modelled proteina??protein interaction (PPI) predicted strong molecular interaction between these two receptors and SARS-CoV-2 spike protein (S1 domain). However, two missense SNPs, rs12329760 (TMPRSS2) and rs1129599 (CD26), were not found to be involved physically in the said interaction. Four regulatory variants (rs112657409, rs11910678, rs77675406 and rs713400) from TMPRSS2 were found to influence the expression of TMPRSS2 and pathologically relevant MX1. rs13015258 a 50 UTR variant from CD26 have significant role in regulation of expression of key regulatory genes that could be involved in SARS-CoV-2 internalization. Overexpression of CD26 through epigenetic modification at rs13015258-C allele was found critical and could explain the higher SARS-CoV-2 infected fatality rate among type 2 diabetes.
机译：目前，200多个国家和地区受冠状病毒疾病-19（Covid-19）大流行的影响。老年人（年龄> 60岁），2型糖尿病和高血压患者，发生率和病例死亡率明显高。细胞受体Ace2，丝氨酸蛋白酶TmpRS2和外肽酶CD26（也称为DPP4）是潜在地涉及SARS-COV-2感染的三个膜结合蛋白。我们假设来自TMPRS2和CD26的常见变体可能在预见的人口或一群人的感染易感性中起重要作用。研究了TMPRSS2和CD26的编码（麦基语）和监管变量在26个全球人口中研究过TMPRSS2和CD26。鉴定了两个畸形和五个监管SNP具有差异等位基因频率。在不同群体中观察到显着的连锁不平衡（LD）签名。模型蛋白质蛋白质相互作用（PPI）预测这两个受体与SARS-COV-2穗蛋白（S1结构域）之间的强分子相互作用。然而，在所述相互作用中，没有发现两个密封SNP，RS12329760（TMPRS2）和RS1129599（CD26）。发现来自TMPRSS2的四种监管变体（RS112657409，RS11910678，RS713400），影响TMPRSS2和病理相关MX1的表达。 RS13015258 A来自CD26的50 utr变体在调节可参与SARS-COV-2内化的关键调节基因的表达中具有重要作用。 CD26过表达CD26通过在RS13015258-C等位基因上进行表观修饰，可以解释2型糖尿病之间的SARS-COV-2受感染的死亡率。

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