These results indicate that TMPRSS6 polymorphisms are more frequent in subjects with persistent IDA than in healthy controls, and in thalassemia carriers V736A variant may account for lower hemoglobin and MCV levels.
Thus, the phenotype associated with the unique combination of mutations uncovered in both patients expands the spectrum of disease associated with TMPRSS6 mutations to include iron deficiency anemia that is accompanied by hyperferritinemia at initial presentation and is responsive to continued oral iron therapy.
Here, we show that iron deficiency anemia with poor intestinal absorption and defective iron utilization of IV iron is caused by inherited mutations in TMPRSS6, a liver-expressed gene that encodes a membrane-bound serine protease of previously unknown role that was recently reported to be a regulator of hepcidin expression.
Our findings suggest that TF, TFR2 and TMPRSS6 polymorphisms are significantly associated with decreased iron status, but only variants in TMPRSS6 are genetic risk factors for iron deficiency and IDA.
Our study suggests homozygosity for TMPRSS6rs855791 C genotype has a protective role against IDA in women at reproductive age, especially in those with menorrhagia.
Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin.
In addition, three children with iron refractory iron deficiency anemia, and one sibling with iron responsive iron deficiency anemia were also examined for polymorphisms or sporadic mutations in TMPRSS6.
Iron supplementation therapeutic management in CD could depend on TMPRSS6 genotype that could predict persistent IDA despite iron supplementation and GFD.
After excluding all known causes responsible for iron deficiency anaemia we searched for mutations in SLC11A2 and TMPRSS6 that could explain the severe anaemia in these children.
The aim of the study was to investigate the association of rs855791, rs4820268, rs5756506, rs2235324, rs2413450, rs2111833, rs228919, and rs733655 SNPs in TMPRSS6 gene with IDA susceptibility and iron-related clinical parameters.
After excluding all known causes responsible for iron deficiency anaemia we searched for mutations in SLC11A2 and TMPRSS6 that could explain the severe anaemia in these children.
To evaluate the association of genetic variants in genes involved in iron delivery and hepcidin regulation pathways with the risk of iron-deficiency anemia (IDA), the following single nucleotide polymorphisms were genotyped in 2139 unrelated elderly Chinese women: rs3811647 (TF), rs7385804 (TFR2), rs235756 (BMP2), and rs855791(V736A) and rs4820268 (TMPRSS6, encoding matriptase-2).
HFE mutations increase iron absorption in patients with haemochromatosis, and the mean transferrin saturations and ferritin levels are mildly increased in heterozygotes, suggesting that HFE mutations may protect against iron depletion and iron deficiency anaemia.
We determined whether the rise in post-prandial serum iron is increased in fully treated patients with hereditary haemochromatosis (HFEC282Y+/+; HH) compared to iron deficiency anaemia (IDA), iron-replete heterozygous subjects (HFEC282Y+/-) and iron-replete controls (HFEC282Y-/-).
Anaemia is common in patients with inflammatory bowel disease [IBD], its two main aetiologies being iron deficiency anaemia [IDA] and anaemia of chronic inflammation [ACI].