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Apolipoprotein A1 Gene Polymorphism and Its Association With TNF-Alpha and Interleukin-6 Levels in Uncomplicated
Bose E Orimadegun1, Adedayo O Faneye2, Georgina N Odaibo2
1Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Insights
Apolipoprotein A1 (APOA1) levels are linked to malaria severity in Nigerian children. Lower APOA1 correlates with higher parasite counts, suggesting its potential as a therapeutic target for malaria.
Area of Science:
- Genetics and Immunology
- Infectious Diseases
- Biochemistry
Background:
- Malaria, particularly Plasmodium falciparum, poses a significant health burden in sub-Saharan Africa, disproportionately affecting children.
- Host genetic factors influence malaria susceptibility and severity, with apolipoprotein A1 (APOA1) showing potential immunomodulatory roles.
- Understanding the interplay between APOA1 gene polymorphisms, APOA1 levels, and inflammatory responses is crucial for malaria management.
Purpose of the Study:
- To investigate the association of APOA1 gene polymorphisms (G-75A and C+83T) with APOA1 levels and inflammatory markers in Nigerian children with malaria.
- To evaluate the relationship between APOA1 levels, inflammatory markers (TNF-α, IL-6), and Plasmodium falciparum parasite burden.
- To explore gender-specific differences in these associations.
Main Methods:
- Cross-sectional study involving 76 children with malaria and 45 healthy controls.
- Genotyping of APOA1 G-75A and C+83T polymorphisms using PCR-RFLP.
- Measurement of serum APOA1, TNF-α, and IL-6 levels via immunoturbidimetric and ELISA assays.
Main Results:
- High frequencies of wild-type APOA1 alleles (GG and CC) were observed; no homozygous mutants.
- Significant differences in APOA1, TNF-α, and IL-6 levels between malaria patients and controls.
- APOA1 levels negatively correlated with parasite counts (r = -0.272, p = 0.018), while TNF-α (r = 0.417, p = 0.001) and IL-6 (r = 0.279, p = 0.017) positively correlated, indicating APOA1's role as a negative acute-phase reactant.
- Gender-specific analyses showed stronger inflammatory responses in males.
Conclusions:
- APOA1 may serve as a negative acute-phase reactant and a potential biomarker in Plasmodium falciparum malaria.
- The study highlights the influence of genetic variations and inflammatory markers on malaria disease severity.
- Findings suggest APOA1 as a potential therapeutic target and inform personalized malaria management strategies.
Abstract:
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.
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