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

Kelvin M Abuga; Kirk A Rockett; John Muthii Muriuki; Oliver Koch; Manfred Nairz; Giorgio Sirugo; Philip Bejon; Dominic P Kwiatkowski; Andrew M Prentice; Sarah H Atkinson

doi:10.12688/wellcomeopenres.15750.2

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

Wellcome Open Res. 2020 Jun 2:5:40. doi: 10.12688/wellcomeopenres.15750.2. eCollection 2020.

Authors

Kelvin M Abuga¹, Kirk A Rockett², John Muthii Muriuki^{1

3}, Oliver Koch⁴, Manfred Nairz⁵, Giorgio Sirugo⁶, Philip Bejon^{1

7}, Dominic P Kwiatkowski^{2

8

9}, Andrew M Prentice¹⁰, Sarah H Atkinson^{1

7

11}

Affiliations

¹ Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Coast, KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
² Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
³ Open University, KEMRI-Wellcome Trust Research Programme - Accredited Research Centre, Kilifi, Kenya.
⁴ Infection Medicine, The University of Edinburgh, Edinburgh, UK.
⁵ Department of Internal Medicine II, Medical University Innsbruck, Innsbruck, Austria.
⁶ Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
⁷ Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁸ Wellcome Sanger Institute, Hinxton, Cambridge, UK.
⁹ Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
¹⁰ Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia.
¹¹ Department of Paediatrics, University of Oxford, Oxford, UK.

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.

Keywords: Africa; IFNG; Interferon-gamma; anaemia; children; ferritin; genetic polymorphisms; hepcidin; iron; iron deficiency; malaria; transferrin saturation; zinc protoporphyrin.

Associated data

figshare/10.6084/m9.figshare.11807277.v6

Abstract

Associated data

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