CACNA2D2 and Hypertension: Natural selection and evolution have a role in blood pressure variability due to varying frequencies of ancestral alleles that regulated salt homeostasis in humans. In a search carried out in the GWAS catalog in 2018, seven candidate genes with an established pathophysiological mechanism pertaining to hypertension were replicated in GWAS, namely ACE1, ACE2, ADRB1, ADRB2, MME, CACNA2D2, and UMOD. This implies that genetic variants concerning hypertension are comparatively more common (>1% in a population), with negligible natural selection in the past populations.