On the other hand, researchers identified that 1,25 dihydroxy vitamin D3 downregulates renin expression; thus, vitamin D deficiency or defects in the VDR signaling might lead to renin overexpression and renin-angiotensin system (RAS) activation that might cause renal and cardiovascular injuries and other detrimental effects (RAS activation in other tissues) [81]. The gene discussed is REN; the disease is vitamin D deficiency.