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

Abstract

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.

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Fig. 1: A simplified cartoon of renin-angiotensin system (RAS) representing the physiology and effect of malaria exposure.

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Acknowledgements

The authors are thankful to the Director ICMR-National Institute of Malaria Research for encouragement and support in preparing the manuscript. We thank the Department of Biotechnology, Kumaun University for the academic support of the Ph.D. program to AT.

Funding

This work was supported by the Indian Council of Medical Research (ICMR), New Delhi [Grant no. fellowship/42/2018-ECD-II], to AD and the Council of Scientific and Industrial Research (CSIR), New Delhi [Grant No.: 09/905 (0017) /2017-EMR-I] to AT.

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AD and AT wrote the first draft, analyzed the data, and edited the manuscript. VP helped in academic support and edited the manuscript. AT and AS made the table. AD and AS made the figures. AS conceived the idea, designed the project critically reviewed, edited, and finalized the manuscript; All authors read and approved the final manuscript to be published.

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Correspondence to Abhinav Sinha.

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De, A., Tiwari, A., Pande, V. et al. Evolutionary trilogy of malaria, angiotensin II and hypertension: deeper insights and the way forward. J Hum Hypertens (2021). https://doi.org/10.1038/s41371-021-00599-0

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