Association of Biochemical and Genetic Level Variations of G6PD in Pathogenesis of Plasmodium Falciparum Infected Malaria Cases: A Study from Dimoria Block of Assam

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common inherited enzymatic disorders and has been implicated in malaria susceptibility and treatment-related haemolysis. However, information on the prevalence of G6PD deficiency and common G6PD gene variants among malaria-endemic tribal populations of Northeast India remains limited. This study investigated the association of biochemical G6PD deficiency and common G6PD genetic variants with Plasmodium falciparum malaria in the Dimoria block of Assam.

Methods: A hospital- and community-based case-control study was conducted involving 153 microscopically confirmed P. falciparum malaria patients (128 uncomplicated and 25 severe malaria cases) and 122 age- and sex-matched healthy controls. G6PD enzyme activity was screened using the fluorescence spot test. Biochemically deficient samples were further analysed for G6PD Orissa (131C>G), G6PD Kerala-Kalyan (949G>A), and G6PD Mediterranean (563C>T) variants by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed using SPSS version 25.0.

Results: Biochemical G6PD deficiency was detected in 17 (11.11%) malaria patients and 8 (6.56%) healthy controls, suggesting a higher prevalence among malaria cases (OR=1.781; 95% CI: 0.741–4.279). Molecular analysis identified only the G6PD Orissa variant in the study population, while the Kerala-Kalyan and Mediterranean variants were absent. The G6PD Orissa variant showed a higher frequency among uncomplicated malaria patients than controls (OR=1.951; 95% CI: 0.351–10.852), although the association did not reach statistical significance. No association was observed with severe malaria.

Conclusions: Biochemical G6PD deficiency and the G6PD Orissa variant were more frequently observed among P. falciparum-infected individuals in this malaria-endemic tribal population of Assam. Although the observed associations were not statistically significant, the findings highlight the importance of G6PD screening before antimalarial therapy and provide baseline genetic epidemiological data for Northeast India. Larger multicentric studies are warranted to validate these observations and to better understand the role of G6PD variants in malaria susceptibility and clinical outcomes.