Association of common variant rs9934336 of SLC5A2 (SGLT2) gene with SARS-CoV-2 infection and mortality

COVID-19 has its life-threatening complications more pronounced in people with underlying health conditions such as diabetes, cardiovascular disease and kidney disease. Inhibition of the sodiumglucose cotransporter 2 (SGLT2), which primarily increases urinary glucose excretion, is shown to be beneficial in patients with type 2 diabetes mellitus (T2D) and other comorbidities. SGLT2 is encoded by SLC5A2 gene, and of the several genetic variants, SNP rs9934336 is gaining importance for being associated with reduced HbA1c level and lower incidence of T2D. Since a complex bidirectional relationship exists between COVID-19 and hyperglycaemia, we conducted a worldwide association study to investigate the effect of rs9934336 on COVID-19 outcomes. Worldwide prevalence data of SLC5A2 SNP rs9934336 were obtained from relevant published articles and databases for genomic variants. COVID-19 data procured from the Worldometer website were used for conducting Spearman's correlation analysis with minor allele frequency data of rs9934336. Significant positive correlation was observed between rs9934336 and COVID-19 incidence (p < 0.0001, r = 0.6225) as well as deaths (p < 0.0001, r = 0.5837). The present finding of significant association of SLC5A2 variant rs9934336 with COVID-19 risk has to be validated by case-control studies in diverse populations along with other variants regulating the expression and function of SGLT2.