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.

中文翻译：

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SLC5A2 (SGLT2) 基因常见变异 rs9934336 与 SARS-CoV-2 感染和死亡率的关联

COVID-19 的危及生命的并发症在患有糖尿病、心血管疾病和肾脏疾病等基础疾病的人群中更为明显。抑制钠葡萄糖协同转运蛋白 2 (SGLT2) 主要增加尿葡萄糖排泄，已被证明对 2 型糖尿病 (T2D) 和其他合并症患者有益。SGLT2 由 SLC5A2 基因编码，在多个遗传变异中，SNP rs9934336 因与 HbA1c 水平降低和 T2D 发病率降低相关而变得越来越重要。由于 COVID-19 和高血糖之间存在复杂的双向关系，我们进行了一项全球关联研究，以调查 rs9934336 对 COVID-19 结果的影响。SLC5A2 SNP rs9934336 的全球患病率数据来自相关已发表的基因组变异文章和数据库。从 Worldometer 网站获取的 COVID-19 数据用于与 rs9934336 的次要等位基因频率数据进行 Spearman 的相关性分析。rs9934336 与 COVID-19 发病率（p < 0.0001，r = 0.6225）以及死亡人数（p < 0.0001，r = 0.5837）之间观察到显着正相关。目前发现 SLC5A2 变体 rs9934336 与 COVID-19 风险存在显着关联，这一发现必须通过不同人群中的病例对照研究以及调节 SGLT2 表达和功能的其他变体进行验证。