**2. ACE2 rs2285666 association with spatial distribution of COVID-19 in India**

Host-pathogen interaction studies have revealed that ACE2 receptor present on the host cell works as a receptor for the spike glycoprotein of SARS-CoV-2 [12]. ACE2 is present on X-chromosome in humans, in which a polymorphism rs2285666 is shown to have significant disparity amongst Europeans and Asians

#### **Figure 1.**

*Srivastava et al. have shown a direct correlation between the rs2285666 polymorphism and ACE2 gene expression.*

*COVID-19 Researches: Where India Stands So Far? DOI: http://dx.doi.org/10.5772/intechopen.96397*

[13, 14]. The decreased expression of ACE2 is frequently associated with increased susceptibility towards the severity of COVID-19 disease. Shrivastava et al. used this information as the principle of their study to find out the frequency of alternate allele (allele T on plus strand or allele A on minus strand) of this single nucleotide variation (SNV) in Indian populations and predict the cause of low infection rate as well as low Case Fatality Rate (CFR) in western states of India (**Figure 1**) [15].

In yet another study they showed that the overall genome of South Asians share greater genetic affinity with West Eurasians, however the ACE2 gene has greater genetic affinity with East Eurasians. The phylogenetic analysis of haplotypes distinctly classifies three types of haplotypes in order to identify the SNP which reveals greater affinity between South Asians and East Eurasians. Out of these three haplotypes- haplotype 3 (ht3) is shown to be harbored by East Eurasians and South Asians and derived from rs2285666 [16]. The ACE2 gene rs2285666 polymorphism is also shown to have association with type 2 diabetes mellitus (T2DM) in which A allele is associated with higher risk of T2DM [17]. The protective role of ACE2 in nephric tubules is shown in several studies, and its reduced expression contributes to the development and progression of kidney injury and diabetic nephropathy is explored by Reich et al. [18]. These studies strengthen the hypothesis of the association of rs2285666 (TT-plus strand or AA-minus strand), which increases the expression of ACE2 receptor protein with lower case fatality rate.
