Submitted June 6, 2008
Accepted August 4, 2008
Tumor necrosis factor SNP haplotypes are associated with iron deficiency anemia in West African children
Sarah H. Atkinson*, Kirk A. Rockett, Gareth Morgan, Philip A. Bejon, Giorgio Sirugo, Maria A. O'Connell, Neil Hanchard, Dominic Kwiatkowski, and Andrew M. Prentice
Department of Paediatrics, University of Oxford, Oxford
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford
MRC Keneba and MRC Laboratories Banjul, MRC, Gambia, Banjul
Genetics Programme, MRC Gambia, Banjul
MRC Human Nutrition Research, MRC, Cambridge
MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, London
* Corresponding author; email: sarah.atkinson{at}paediatrics.ox.ac.uk.
Plasma levels of tumor necrosis factor 
(TNF-) are significantly raised in malaria infection and TNF- is thought to inhibit intestinal iron absorption and macrophage iron release. This study investigated putative functional single nucleotide polymorphisms (SNPs) and haplotypes across the major histocompatibility complex (MHC) class III region, including TNF and its immediate neighbors nuclear factor of 
light polypeptide gene enhancer in B cells (lBL), inhibitor like 1 and lymphotoxin alpha (LTA), in relation to nutritional iron status and anemia in a cohort of 780 children across a malaria season. The prevalence of iron deficiency anemia (IDA) increased over the malaria season (P<0.0001). The TNF-308 AA genotype was associated with an increased risk of iron deficiency (adj. OR 8.1; P = 0.001) and IDA (adj. OR 5.1; P = 0.01) at the end of the malaria season. No genotypes were associated with IDA prior to the malaria season. Thus, TNF- appears to be a risk factor for iron deficiency and IDA in children in a malaria-endemic environment and this is likely to be due to a TNF--induced block in iron absorption.
