Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among various ethnic populations
Genetic variability of human angiotensin-converting enzyme 2 (hACE2) among various ethnic populations
复制标题
DOI：
10.1002/mgg3.1344
复制
发表时间：
2020-06-18
影响因子：
2
通讯作者：
Rahman, Proton
中科院分区：
文献类型：
--
作者：
Li, Quan;Cao, Zanxia;Rahman, Proton
背景新冠肺炎感染的易感性、严重性和死亡率似乎存在很大的地区差异。许多潜在因素可以解释各国之间感染和死亡人数的巨大差异。我们研究了人类血管紧张素转换酶2(HACE2)基因的遗传差异，因为它的受体是SARS-CoV-2的细胞入口。目前，关于ACE2基因多态性和表达水平在不同种族之间的差异的数据很少。方法比较欧洲人和东亚人突变的等位基因频率。通过分子动力学模拟研究了突变体对蛋白质结构的影响。计算了S蛋白与hACE2的结合自由能。我们还检测了来自HapMap3的八个全球种群中hACE2基因的表达。结果4个错义突变的等位基因频率在亚洲人和高加索人之间存在显著差异。分子动力学研究表明，其中两个变异株(K26R和I468V)可能影响病毒S蛋白与hACE2受体的结合特性。我们还注意到，与中国人相比，HapMap3中一些群体的基因表达略有不同。结论我们的研究揭示了hACE2基因在不同人群之间的微妙变化，但由于缺乏进一步的体外和功能研究，这种差异的幅度很小，其意义尚不清楚。
Background There appears to be large regional variation for susceptibility, severity, and mortality for COVID-19 infections. Numerous potential factors could explain the wide variability in the number of infections and death among the countries. We examined genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS-CoV-2. At present, there is a paucity of data regarding the differences for ACE2 polymorphisms and expression levels between ethnicities. Methods We compared the allele frequency of mutations between European and East Asians. Molecular dynamic simulation were performed to investigate the influences of significant mutant on protein structure. The binding free energies were calculated between S protein and hACE2. We also examined hACE2 gene expression in eight global populations from HapMap3. Results Four missense mutations showed significant minor allele frequency difference between Asians and Caucasians. Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. We also noted marginal differences in gene expression for some populations in HapMap3 as compared to the Chinese population. Conclusion Our studies reveal subtle changes in the genetics of hACE2 between human populations, but the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies.