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

Wellcome Open Research

article

Kelvin M. Abuga¹  Kirk A. Rockett²  John Muthii Muriuki¹  Oliver Koch⁴  Manfred Nairz⁵  Giorgio Sirugo⁶  Philip Bejon¹  Dominic P. Kwiatkowski²  Andrew M. Prentice^1,10  Sarah H. Atkinson¹ 

[1] Kenya Medical Research Institute ,(KEMRI) Centre for Geographic Medicine Coast, KEMRI-Wellcome Trust Research Programme;Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford;Open University, KEMRI-Wellcome Trust Research Programme – Accredited Research Centre;Infection Medicine, The University of Edinburgh;Department of Internal Medicine II, Medical University Innsbruck;Perelman School of Medicine, University of Pennsylvania;Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford;Wellcome Sanger Institute;Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford;Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine;Department of Paediatrics, University of Oxford

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

DOI  :  10.12688/wellcomeopenres.15750.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

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 ofIFNG 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 theIFNG 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 fiveIFNG haplotype-tagging SNPs (IFNG-1616 [rs2069705],IFNG+874 [rs2430561],IFNG+2200 [rs1861493],IFNG+3234 [rs2069718] andIFNG+5612 [rs2069728]). TheIFNG+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 byIFNG+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 linkingIFNG 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.

【 授权许可】

CC BY