Unravelling the Influence of Host Genetic Factors on Malaria Susceptibility in Asian Populations.
Gupta A., Skjefte M., Muppidi P., Sikka R., Pandey M., Bharti PK., Gupta H.
Malaria is a deadly blood-borne disease caused by a Plasmodium parasite. Infection results in various forms of malaria, including an asymptomatic state, uncomplicated disease, or severe disease. Severe malaria (SM) is particularly prevalent among young children and is a significant cause of mortality. SM is associated with the sequestration of parasitized erythrocytes in the microvasculature of vital host organs, disrupting the normal functioning of the immune system. Although the exact mechanisms of malaria pathogenesis are yet to be fully understood, researchers have been investigating the role of host genetics in determining the severity of the disease and the outcome of infection. The objective of this study is to identify specific host genes that have been examined for their association with malaria in Asian populations and pinpoint those most likely to influence susceptibility. Through an extensive screening process, a total of 982 articles were initially identified, and after careful review, 40 articles discussing 68 genes were included in this review. By constructing a network of protein-protein interactions (PPIs), we identified six key proteins (TNF, IL6, TLR4, IL1β, IL10, and IL8) that exhibited substantial interactions (more than 30 edges), suggesting their potential as significant targets for influencing malaria susceptibility. Notably, these six proteins have been previously identified as crucial components of the immune response, associated with malaria susceptibility, and capable of affecting different clinical forms of the disease. Identifying genes that contribute to malaria susceptibility or resistance holds the promise of enhancing the diagnosis and treatment of this debilitating illness. Such knowledge has the potential to pave the way for more targeted and effective strategies in combating malaria, particularly in Asian populations where controlling Plasmodium vivax is challenging, and India contributes the highest number of cases. By understanding the genetic factors underlying malaria vulnerability, we can develop interventions that are tailored to the specific needs of Asian populations, ultimately leading to better outcomes in the fight against this disease.