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Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children
Kelvin M Abuga1, Kirk A Rockett2, John Muthii Muriuki1,3
1Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
Insights
Genetic variants in the Interferon-gamma (IFN-γ) gene showed limited association with iron deficiency and anaemia risk in Gambian children. Further research is needed to clarify the role of genetically influenced IFN-γ levels in these conditions.
Area of Science:
- Genetics
- Immunology
- Pediatrics
- Nutritional Science
Background:
- Anaemia is a significant public health issue in African children, particularly in malaria-endemic regions.
- Interferon-gamma (IFN-γ), elevated during malaria, may affect iron status and red blood cell production.
- Genetic variations in the IFN-γ gene (IFNG) can influence IFN-γ production.
Purpose of the Study:
- To investigate the association between IFNG gene polymorphisms and haplotypes with iron status and anaemia in Gambian children.
- To explore the functional impact of specific IFNG SNPs on haemoglobin levels and iron deficiency markers.
Main Methods:
- Genotyping of five IFNG haplotype-tagging SNPs (rs2069705, rs2430561, rs1861493, rs2069718, rs2069728) in 780 Gambian children (2-6 years).
- Measurement of haemoglobin, iron status biomarkers, and inflammation markers at the beginning and end of the malaria season.
- Statistical analysis using multivariable models adjusted for confounders including age, sex, village, inflammation, and malaria parasitaemia.
Main Results:
- The IFNG+2200C allele (rs1861493) was linked to lower haemoglobin concentrations and a trend towards iron deficiency at the end of the malaria season.
- A specific IFNG haplotype carrying the +2200C allele showed similar associations with reduced haemoglobin and increased risk of iron deficiency and anaemia.
- Limited statistical evidence was found overall linking IFNG polymorphisms to increased risk of iron deficiency and anaemia.
Conclusions:
- IFNG polymorphisms demonstrated a limited association with the risk of developing iron deficiency and anaemia in the studied Gambian children.
- Further comprehensive studies are required to elucidate the precise effects of genetically determined IFN-γ levels on iron deficiency and anaemia risk in children in malaria-endemic areas.
Abstract:
Background: Anaemia is a major public health concern especially in African children living in malaria-endemic regions. Interferon-gamma (IFN-γ) is elevated during malaria infection and is thought to influence erythropoiesis and iron status. Genetic variants in the IFN-γ gene (IFNG) are associated with increased IFN-γ production. We investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes of IFNG in relation to nutritional iron status and anaemia in Gambian children over a malaria season. Methods: We used previously available data from Gambian family trios to determine informative SNPs and then used the Agena Bioscience MassArray platform to type five SNPs from the IFNG gene in a cohort of 780 Gambian children aged 2-6 years. We also measured haemoglobin and biomarkers of iron status and inflammation at the start and end of a malaria season. Results: We identified five IFNG haplotype-tagging SNPs ( IFNG-1616 [rs2069705], IFNG+874 [rs2430561], IFNG+2200 [rs1861493], IFNG+3234 [rs2069718] and IFNG+5612 [rs2069728]). The IFNG+2200C [rs1861493] allele was associated with reduced haemoglobin concentrations (adjusted β -0.44 [95% CI -0.75, -0.12]; Bonferroni adjusted P = 0.03) and a trend towards iron deficiency compared to wild-type at the end of the malaria season in multivariable models adjusted for potential confounders. A haplotype uniquely identified by IFNG+2200C was similarly associated with reduced haemoglobin levels and trends towards iron deficiency, anaemia and iron deficiency anaemia at the end of the malaria season in models adjusted for age, sex, village, inflammation and malaria parasitaemia. Conclusion: We found limited statistical evidence linking IFNG polymorphisms with a risk of developing iron deficiency and anaemia in Gambian children. More definitive studies are needed to investigate the effects of genetically influenced IFN-γ levels on the risk of iron deficiency and anaemia in children living in malaria-endemic areas.
