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

<p><strong>Background:</strong> 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 t...

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Main Authors: Abuga, K, Rockett, K, Muriuki, JM, Koch, O, Nairz, M, Sirugo, G, Bejon, P, Kwiatkowski, D, Prentice, A, Atkinson, S
Format: Journal article
Language:English
Published: F1000 Research 2020
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author Abuga, K
Rockett, K
Muriuki, JM
Koch, O
Nairz, M
Sirugo, G
Bejon, P
Kwiatkowski, D
Prentice, A
Atkinson, S
author_facet Abuga, K
Rockett, K
Muriuki, JM
Koch, O
Nairz, M
Sirugo, G
Bejon, P
Kwiatkowski, D
Prentice, A
Atkinson, S
author_sort Abuga, K
collection OXFORD
description <p><strong>Background:</strong> 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.</p> <p><strong>Methods:</strong> 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.</p> <p><strong>Results:</strong> 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.</p> <p><strong>Conclusion:</strong> 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.</p>
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spelling oxford-uuid:60b823ca-765f-466e-ab36-4a4dce0d70b92022-03-26T17:55:06ZInterferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian childrenJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:60b823ca-765f-466e-ab36-4a4dce0d70b9EnglishSymplectic ElementsF1000 Research2020Abuga, KRockett, KMuriuki, JMKoch, ONairz, MSirugo, GBejon, PKwiatkowski, DPrentice, AAtkinson, S<p><strong>Background:</strong> 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.</p> <p><strong>Methods:</strong> 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.</p> <p><strong>Results:</strong> 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.</p> <p><strong>Conclusion:</strong> 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.</p>
spellingShingle Abuga, K
Rockett, K
Muriuki, JM
Koch, O
Nairz, M
Sirugo, G
Bejon, P
Kwiatkowski, D
Prentice, A
Atkinson, S
Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children
title Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children
title_full Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children
title_fullStr Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children
title_full_unstemmed Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children
title_short Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children
title_sort interferon gamma polymorphisms and risk of iron deficiency and anaemia in gambian children
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AT kocho interferongammapolymorphismsandriskofirondeficiencyandanaemiaingambianchildren
AT nairzm interferongammapolymorphismsandriskofirondeficiencyandanaemiaingambianchildren
AT sirugog interferongammapolymorphismsandriskofirondeficiencyandanaemiaingambianchildren
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