REN and cardiovascular disorder: There is evidence showing the renin-angiotensin system is activated in OC-induced hypertension but it is unclear how estrogen interacts with it and if there are protective genetic factors. The T235M polymorphism was previously associated with preeclampsia and essential hypertension. Polymorphisms in the promoter region of the angiotensinogen gene have been associated with essential hypertension. Alleles in the ACE insertion/deletion polymorphism were associated with cardiovascular disease.