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.
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.
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-alpha-induced block in iron absorption.
In general screening of populations with ATT, BTT and HET, we propose that hypochromic individuals be first identified by MCH <26 pg and carriers distinguished within these hypochromic individuals from IDA by using RBC-Y/MCV.
We evaluated the use of RBC-Y in 156 normal individuals and 332 patients; ATT (n = 37), BTT (n = 61), HET (n = 25), HbH disease (n = 5), ACD (n = 67), IDA (n = 83) and ACD with IDA (n = 54).
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.
refractory iron-deficiency anemia has a multifactorial origin related to various gastrointestinal conditions, with celiac disease plus malabsorption and IBD together with isolated gluten intolerance being most common.
Such a genetic positive selection is represented by the HEF C282Y mutation of hemochromatosis, SH2B3 loci and the HLA celiac disease-associated repertoire, enabling the celiac to overcome iron deficiency anemia and micro pathogen richness, respectively.
DMT1, ferroportin and TFR1 mRNA levels were significantly increased in post-phlebotomized hemochromatics relative to controls. mRNAs of all tested molecules were significantly increased in patients with IDA compared to controls.
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.
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).
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).
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.
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.
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.
Extended analysis of an association observed between MCH and the alpha-globin gene cluster variants demonstrated independent effects and epistatic interaction at the locus, impacting the risk of iron deficiency anemia in African Americans with specific genotype states.
Extended analysis of an association observed between MCH and the alpha-globin gene cluster variants demonstrated independent effects and epistatic interaction at the locus, impacting the risk of iron deficiency anemia in African Americans with specific genotype states.