Evolutionary trilogy of malaria, angiotensin II and hypertension: deeper insights and the way forward

Despite clinical and pathological distinctions between malaria and hypertension, accumulated epidemiological and evolutionary evidence indicate the need of deeper understanding how severe malaria contributes to elevated hypertension risk. Malaria is said to exert strong selection pressure on the host genome, thus selecting certain genetic polymorphisms. Few candidate polymorphisms have also been reported in the RAS (ACE I/D and ACE2 rs2106809) that are shown to increase angiotensin II (ang II) levels in a combinatorial manner. The raised ang II has some antiplasmodial actions in addition to protecting against severe/cerebral malaria. It is hypothesized that RAS polymorphisms may have been naturally selected over time in the malaria-endemic areas in such a way that hypertension, or the risk thereof, is higher in such areas as compared to non-malaria endemic areas. The purpose of this review is to gain deeper insights into various sparse evidence linking malaria and hypertension and suggesting a way forward.