What question did this study set out to answer?

This research aims to determine the association between G6PD deficiency variants and Filipino β-thalassemia with the risk of Plasmodium knowlesi infection.

April 17, 2026Open Access

G6PD variants but not Filipino beta-thalassemia are associated with reduced risk of Plasmodium knowlesi infection in Sabah, Malaysia

Puntos clave

This research aims to determine the association between G6PD deficiency variants and Filipino β-thalassemia with the risk of Plasmodium knowlesi infection.
Retrospective case-control design comparing PCR-confirmed P. knowlesi cases with controls
Genotyping employed multiplex PCR for G6PD variants and gap-PCR for β-thalassemia deletions
Statistical analyses utilized Fisher’s exact tests and logistic regression models to assess risk associations
G6PD deficiency variants present in 3.8% of P. knowlesi cases compared to 12.4% of controls (OR = 0.28, p = 0.034)
Predominant G6PD variant was Viangchan (71%)
No significant association found between Filipino β-thalassemia and malaria risk
G6PD variants confer considerable protection against P. knowlesi susceptibility

Resumen

The emergence of Plasmodium knowlesi as the predominant cause of malaria in Malaysian Borneo raises important questions about protective genetic factors in endemic populations. This study investigates two common erythrocyte polymorphisms, glucose-6-phosphate dehydrogenase (G6PD) deficiency and Filipino β-thalassemia, for association with P. knowlesi infection risk. A retrospective case–control study compared 106 PCR-confirmed P. knowlesi cases with 89 controls from Sabah, Malaysia. Genotyping used multiplex PCR (8 major Southeast Asian G6PD variants) and gap-PCR (Filipino β-thalassemia deletions). Statistical analysis employed Fisher’s exact tests and logistic regression models to evaluate associations with infection risk, including controlling for age, sex, ethnicity and district site. G6PD deficiency genetic variants were present in 4/106 (3.8%, 95%CI 1.0–9.4%) P. knowlesi cases compared to 11/89 (12.4%, 95%CI 6.3–21.0%) controls (OR = 0.28, 95%CI 0.09–0.91; p = 0.034). The Viangchan variant (871G>A) was predominant (71%), with Coimbra and Mediterranean variants also present. No relationship with G6PD variants and severe malaria or sex was detected, although analysis was constrained by small numbers. Filipino β-thalassemia demonstrated no association. G6PD deficiency related variants confer substantial protection against P. knowlesi susceptibility, while β-thalassemia appears neutral. Findings have implications for zoonotic malaria transmission risk in Southeast Asia.

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