Iron deficiency is considered the most common nutritional deficiency worldwide and affects children and women in both non-industrialized as well as industrialized countries. The main regulatory molecule of iron metabolism is hepcidin, a hormone produced in the liver that regulates intestinal iron absorption, placental transport, recycling of iron by macrophages and release from stores. The expression of hepcidin is regulated by many mediators, one of which is Matriptase-2 - a transmembrane protease. Complete loss of function leads to the rare disease iron-refractory iron deficiency anemia (IRIDA). Matriptase-2 is encoded by the gene TMPRSS6 and the single nucleotide polymorphism (SNP) rs855791 causes a non-synonymous substitution (V736A) that reduces the activity of the protease to inhibit hepcidin transcription. Genome wide association studies have identified the TMPRSS6 SNP rs855791 has a strong association with red blood cell and iron parameters in the general population. The objectives of the study is to measure oral iron absorption and systemic iron utilization into red blood cells (RBC) using oral isotopic labels in subjects homozygotes for common variants of the TMPRSS6 gene with the SNP rs855791 (A736V); AA vs. VV subjects. The aim is to conduct an iron absorption study in 80 Taiwanese women of reproductive age, non-pregnant, non-anemic, investigating the effect of the genetic variants of the SNP rs855791. The participants will be split in two groups of equal size; wild type AA vs. mutation VV. Iron absorption and systemic utilization will be assessed by two test meals containing stable isotopes of iron.The primary outcome of the trial is the oral iron absorption from a test meal as compared between the two genotypes AA vs. VV. Secondary outcomes are the comparison iron status markers between the two genotypes.

NCT03317873

Conditions

1. Iron Metabolism Disorders

Interventions

1. Dietary Supplement: Testmeal A
2. Dietary Supplement: Testmeal B

MeSH:Metabolic Diseases Iron Metabolism Disorders

The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study.

The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study Iron deficiency is considered the most common nutritional deficiency worldwide and affects children and women in both non-industrialized as well as industrialized countries.

Matriptase-2 is encoded by the gene TMPRSS6 and the single nucleotide polymorphism (SNP) rs855791 causes a non-synonymous substitution (V736A) that reduces the activity of the protease to inhibit hepcidin transcription.

Genome wide association studies have identified the TMPRSS6 SNP rs855791 has a strong association with red blood cell and iron parameters in the general population.

The objectives of the study is to measure oral iron absorption and systemic iron utilization into red blood cells (RBC) using oral isotopic labels in subjects homozygotes for common variants of the TMPRSS6 gene with the SNP rs855791 (A736V); AA vs. VV subjects.

The aim is to conduct an iron absorption study in 80 Taiwanese women of reproductive age, non-pregnant, non-anemic, investigating the effect of the genetic variants of the SNP rs855791.

fasting concentrations of plasma hepcidin in AA and VV variants of SNP rs855791.

The difference in fasting concentrations of serum iron, transferrin saturation, serum ferritin, hemoglobin, erythrocyte volume in AA and VV variants of SNP rs855791.

Inclusion Criteria: - Subjects homozygotous for the for AA (CC), or VV (TT) variant of the SNP rs855791 of the TMPRSS6 gene.

- Use of long-term medication during the study - Subjects that will take part of another clinical study at the same time or had within the last 30 days before the first study day - Intake of mineral/vitamin supplements 2 weeks before the first study day and during the study Inclusion Criteria: - Subjects homozygotous for the for AA (CC), or VV (TT) variant of the SNP rs855791 of the TMPRSS6 gene.

Anaemia continues to be one of the most common health problems affecting children and pregnant women in low-income countries. Nutritional iron deficiency is believed to be the main driver of anaemia, so mass iron supplementation and food fortification programs have been recommended by most public health organizations. However, these interventions are frequently ineffective and new strategies are desperately needed. Both anaemia and iron absorption are influenced by multiple factors, including nutritional status, infection, low grade inflammation and host genetics. The discovery of hepcidin, the master regulator of iron absorption and regulation has opened new avenues for investigation. Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) within hepcidin regulatory genes that are associated with altered iron status both in African populations. The study aims to investigate the impact of genetic alterations in hepcidin regulation on oral iron absorption. A recall-by-genotype study will be conducted using an existing database of pre-genotype individuals in rural Gambia (West Kiang). This database comprise of data on >3000 Gambians, with Illumina HumanExome array data on 80K directly genotyped putative functional variants as well as imputation data on 20M variants.

NCT03341338

Conditions

1. Anemia

To begin with, the focus will be on three common SNPs within the TMPRSS6 gene, rs855791, rs4820268 and rs2235321, with minor allele frequencies (MAF) at 7, 27 and 44% in the study population.