Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children

<ns7:p><ns7:bold>Background</ns7:bold>: 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 <ns7:italic>(IFNG</ns7:italic>) are associated with increased IFN-γ production. We investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes of<ns7:italic> IFNG</ns7:italic> in relation to nutritional iron status and anaemia in Gambian children over a malaria season.</ns7:p><ns7:p> </ns7:p><ns7:p> <ns7:bold>Methods: </ns7:bold>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<ns7:italic> IFNG</ns7:italic> gene in a cohort of 780 Gambian children. We also measured haemoglobin and biomarkers of iron status and inflammation at the start and end of a malaria season.</ns7:p><ns7:p> </ns7:p><ns7:p> <ns7:bold>Results: </ns7:bold>We identified five<ns7:italic> IFNG</ns7:italic> haplotype-tagging SNPs (<ns7:italic>IFNG</ns7:italic>-1616 [rs2069705],<ns7:italic> IFNG</ns7:italic>+874 [rs2430561],<ns7:italic> IFNG</ns7:italic>+2200 [rs1861493], <ns7:italic>IFNG</ns7:italic>+3234 [rs2069718] and<ns7:italic> IFNG</ns7:italic>+5612 [rs2069728]). The<ns7:italic> IFNG</ns7:italic>+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<ns7:italic> IFNG</ns7:italic>+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.</ns7:p><ns7:p> </ns7:p><ns7:p> <ns7:bold>Conclusion:</ns7:bold> We found limited statistical evidence linking<ns7:italic> IFNG</ns7:italic> 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.</ns7:p>