Effects of host genetic variations on response to, susceptibility and severity of respiratory infections

Abstract

The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global crisis, necessitating the identification of genetic factors that modulate the risk of disorder or its severity. The current data about the role of genetic risk factors in determination of rate of SARS-CoV-2 infection in each ethnic group and the severity of disorder is limited. Moreover, several confounding parameters such as the number of tests performed in each country, the structure of the population especially the age distribution, the presence of risk factors for respiratory disorders such as smoking and other environmental factors might be involved in the variability in disease course or prevalence of infection among different ethnic groups. However, assessment of the role of genetic variants in determination of the course of other respiratory infections might help in recognition of possible candidate for further analysis in patients affected with SARS-CoV-2. In the current review, we summarize the data showing the association between genomic variants and risk of acute respiratory distress syndrome, respiratory infections or severity of these conditions with an especial focus on the SARS-CoV-2.

Keywords: ACE; COVID-19; SARS-CoV-2; genetic; respiratory tract infection; single nucleotide polymorphism.

Fig. 1

ACE2 gene is located on chromosome X, in a genomic region which escapes from X inactivation. Yet, it has a heterogeneous sex bias expression in different tissues [5]. The AA genotype of the rs2285666 is associated with higher expression of ACE2. Based on the role of ACE2 as the cell receptor for entrance of the virus, the mentioned polymorphism might affect the infection course [1]. The rs1024611 is located in the transcript start site of the CCL2 gene and might affect expression of the corresponding gene. The GG genotype of this polymorphism is associated with higher levels of CCL2. CCL2 is a chemokine that regulates chemotaxis and secretion of inflammatory mediators from monocytes and macrophages [7]. The rs2070874 polymorphism is located in the 5' UTR of IL-4 gene and might influence transcription of this gene [8]. IL-4 down-regulates ACE2 receptor, thus preclude SARS-CoV entrance into the cells [9].