Our results provide a new pathological EGR1/ADAM10 pathway in sepsis based on the exact genetic association: the rs653765 G→A variants modulate ADAM10 promoter activity by altering binding of the EGR1 transcription factor (TF) to the ADAM10 promoter and then functionally activate ADAM10 gene expression, concomitantly elevating relevant substrates. Here, EGR1 is linked to Sepsis.