Characterization of the ATP2B gene family in blood pressure

The 12q21 locus, which lies near the plasma membrane calcium-transporting ATPase 1 gene (ATP2B1), has one of the strongest associations with blood pressure and hypertension in Europeans and Asians. We performed an association analysis of the ATP2B isomers ATP2B2, ATP2B3, and ATP2B4 with blood pressure and hypertension in 7,551 Korean individuals and observed a link with ATP2B2 and ATP2B4. To examine the regulation of blood pressure by ATP2B, ATP2B1 and ATP2B4 mRNA was reduced in vascular smooth muscle cells by siRNA. The expression pattern of 23 ATP2B-related genes was analyzed by quantitative real-time PCR, which differed between treatment with ATP2B1 and ATP2B4 siRNA. The reduction inATP2B1 mRNA induced a significant change in mRNA levels in the calcium pump RYR1 and the ATP2B-binding protein HOMER1. Conversely, the decrease in ATP2B4 mRNA significantly altered mRNA expression of the calcium pump SLC8A1 and the ATP2B-binding proteins CASK and DLG4. These results suggest that blood pressure is differentially regulated through calcium signaling between ATP2B1 and ATP2B4.