<ns4:p><ns4:bold>Background</ns4:bold>: Oral iron supplementation is commonly used to treat and prevent anaemia. The transmembrane protease serine 6 gene (<ns4:italic>TMPRSS6</ns4:italic>)<ns4:italic>, </ns4:italic>which encodes matriptase 2, is a negative regulator of hepcidin, the key controller of iron homeostasis. Genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) in the <ns4:italic>TMPRSS6</ns4:italic> gene that are associated with an increased risk of iron-deficiency anaemia.  We will investigate the <ns4:italic>in vivo</ns4:italic> effects of three previously reported <ns4:italic>TMPRSS6 </ns4:italic>variants (rs855791, rs4820268 and rs2235321) on oral iron absorption in non-anaemic volunteers in The Gambia.</ns4:p><ns4:p> <ns4:bold>Methods: </ns4:bold>A recall-by-genotype study design will be employed. Pre-genotyped participants will be recruited from the West African BioResouce (WABR), which currently contains over 3000 genotyped individuals. Male and female volunteers will be selected based on polymorphisms (rs855791, rs4820268 and rs2235321) in the <ns4:italic>TMPRSS6 </ns4:italic>gene in the Gambian population. The effects of a single variant allele at one SNP and the additive effect of two or three variant alleles from either two or all three SNPs will be investigated. Study participants will be given a single oral dose of 400mg ferrous sulfate, and blood samples will be collected at baseline, two hours and five hours post supplementation. Differences in iron absorption between genotype groups will be assessed by measuring the increase in serum iron concentration at five hours post iron ingestion.</ns4:p><ns4:p> <ns4:bold>Discussion: </ns4:bold>This study will increase understanding of the role of genetic variations in <ns4:italic>TMPRSS6</ns4:italic> on oral iron absorption in subjects of West African origin. This will test for the biological basis for the association of each of the three <ns4:italic>TMPRSS6</ns4:italic> variants with iron absorption. This may help in guiding future iron intervention strategies, particularly in populations with a high frequency of these SNPs and a high frequency of anaemia.</ns4:p><ns4:p> <ns4:bold>Study</ns4:bold> <ns4:bold>registration</ns4:bold>: ClinicalTrials.gov <ns4:ext-link xmlns:ns5="http://www.w3.org/1999/xlink" ext-link-type="uri" ns5:href="https://clinicaltrials.gov/ct2/show/NCT03341338">NCT03341338</ns4:ext-link> 14/11/17.</ns4:p>