Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka 1000, Bangladesh.
Department of Mathematics and Natural Sciences, Brac University, Dhaka 1212, Bangladesh.
Infect Genet Evol. 2021 Aug;92:104888. doi: 10.1016/j.meegid.2021.104888. Epub 2021 Apr 30.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mediated Coronavirus disease-19 (COVID-19) has affected millions of individuals around all corners of the globe. Symptoms and severities of infection with this highly contagious virus vary among individuals and there is disparity in the number of COVID-19-related casualties across different ethnic groups. The primary receptor for SARS-CoV-2 entry into the host cells is angiotensin-converting enzyme 2 (ACE2). Certain variants of ACE2 are known to be associated with COVID-19 comorbidities such as hypertension, cardiovascular complications, diabetes, chronic lung disease, etc. In this study, we looked into the geographic distribution of disease-associated variants of ACE2 as well as closely located PIR gene to explore any possible correlation with the disparities in COVID-19 severities and casualties across ethnic groups. Frequencies of the ACE2 variants associated with COVID-19 comorbidities are higher in the European and the admixed American populations. These variants are also present with stronger pairwise linkage disequilibrium (LD) in the European and the admixed American populations. On the other hand, the variants with protective role are more prevalent in the East and the South Asian populations. Strong pairwise LD exists among the activity modifying (modifier) variants of the PIR and ACE2 genes only in the European super-population. Absence of these PIR variants in the South Asian population may contribute to the overall lower COVID-19 case fatality rates (CFR) despite the dense population in this region.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）介导的新型冠状病毒病 19（COVID-19）已影响到全球各地的数百万人。这种高传染性病毒在个体中的感染症状和严重程度各不相同，不同种族群体中 COVID-19 相关死亡人数也存在差异。SARS-CoV-2 进入宿主细胞的主要受体是血管紧张素转换酶 2（ACE2）。某些 ACE2 的变体已知与 COVID-19 的合并症有关，例如高血压、心血管并发症、糖尿病、慢性肺病等。在这项研究中，我们研究了与疾病相关的 ACE2 变体以及紧密相邻的 PIR 基因在地理上的分布，以探索与不同种族群体 COVID-19 严重程度和死亡率差异之间可能存在的任何关联。与 COVID-19 合并症相关的 ACE2 变体在欧洲和混合人群中的频率更高。这些变体在欧洲和混合人群中也存在更强的成对连锁不平衡（LD）。另一方面，具有保护作用的变体在东亚和南亚人群中更为普遍。只有在欧洲超级人群中，PIR 和 ACE2 基因的活性修饰（修饰）变体之间才存在强烈的成对 LD。这些 PIR 变体在南亚人群中的缺失可能导致该地区尽管人口密集，但 COVID-19 病死率（CFR）总体较低。
