REN and hypertensive disorder: Furthermore, HSD11B2 gene promoter methylation is associated with HTN onset [58], as well as hypomethylation of genes of the renin-angiotensin-aldosterone (RAA) system or NKCC1 (Na-K-Cl co-transporter 1) gene respectively affect the response to ACE (angiotensin-converting enzyme) inhibitors and diuretics [59,60].