Tumor necrosis factor SNP haplotypes are associated with iron deficiency anemia in West African children Running head: TNF and iron deficiency anemia

Plasma levels of tumor necrosis factor α (TNF-α) are significantly raised in malaria infection and TNF-α 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 κ light polypeptide gene enhancer in B cells (lκBL), 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-α 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-α-induced block in iron absorption. For personal use only. on June 9, 2017. by guest www.bloodjournal.org From