We found a 12T-insertion (ins) polymorphism involving a poly-T sequence (38T vs 26T) within the ATP1A1 5’-regulatory region that is associated with decreased susceptibility to essential hypertension in a male Sardinian cohort, and causes decreased ATP1A1 transcriptional activity, hence decreased ATP1A1 expression, in in vitro reporter-assays compared with the ATP1A1 promoter containing the 12T-deletion. The gene discussed is ATP1A1; the disease is essential hypertension.