Apolipoprotein A1 Gene Polymorphism and Its Association With TNF-Alpha and Interleukin-6 Levels in Uncomplicated Plasmodium Falciparum Malaria in Nigerian Children.
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Malaria remains a significant health challenge, particularly in sub-Saharan Africa, where it contributes substantially to morbidity and mortality among children. The role of genetic polymorphisms in modulating host responses to malaria has gained attention, with apolipoprotein A1 (APOA1) emerging as a candidate due to its anti-inflammatory and immunomodulatory properties. This study investigates the association between two APOA1 gene polymorphisms (G-75A and C+83T), APOA1 levels, and inflammatory markers (tumor necrosis factor-alpha and interleukin-6) in Nigerian children with uncomplicated Plasmodium falciparum malaria. In this cross-sectional study, 76 children with malaria and 45 healthy controls were recruited. Participants were genotyped for G-75A and C+83T polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. Serum levels of APOA1, interleukin-6, and tumor necrosis factor-alpha were measured using immunoturbidimetric and enzyme-linked immunosorbent assays. Statistical analysis assessed genotype frequencies, inflammatory marker levels, and their associations with parasite burden. The G-75A and C+83T polymorphisms exhibited high frequencies of wild-type alleles (GG and CC, respectively) with no homozygous mutant genotypes observed. APOA1 and inflammatory marker levels differed significantly between children with malaria and controls. APOA1 levels negatively correlated with parasite counts (r = -0.272, p = 0.018), suggesting its role as a negative acute-phase reactant. Tumor necrosis factor-alpha and interleukin-6 levels positively correlated with parasite burden (r = 0.417, p = 0.001 and r = 0.279, p = 0.017, respectively), reflecting their roles in malaria pathogenesis. Gender-specific analysis revealed distinct patterns in biomarker correlations, with males showing stronger inflammatory responses. This study underscores the potential role of APOA1 as a biomarker and therapeutic target in malaria, highlighting the influence of genetic and inflammatory factors on disease severity. These findings provide insights into host-pathogen interactions and may inform personalized strategies for managing malaria in endemic regions.