Correlates of Hepcidin and NTBI according to &lt;b&gt;&lt;i&gt;HFE&lt;/i&gt;&lt;/b&gt; Status in Patients Referred to a Liver Centre

Ryan, Eleanor; Ryan, John D.; Russell, Jennifer; Coughlan, Barbara; Tjalsma, Harold; Swinkels, Dorine W.; Stewart, Stephen; Crowe, J.

doi:10.1159/000363490

Cited by 8 publications

(11 citation statements)

References 35 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even though the plasma levels of NTBI are normally very low, this pool increases significantly under conditions of iron overload. The plasma levels of NTBI increase substantially in various diseases related to iron overload, which include genetic disorders such as sickle cell disease and thalassemia 33 , 34 and hemochromatosis 35 , 36 . The increase is also seen in various conditions associated with defective erythropoiesis (myelodysplastic syndromes) 37 and repeated blood transfusion 38 .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells

Ogura

Babu

Miyauchi

et al. 2018

Sci Rep

View full text Add to dashboard Cite

NaCT is a Na+-coupled transporter for citrate expressed in hepatocytes and neurons. It is the mammalian ortholog of INDY (I’m Not Dead Yet), a transporter which modifies lifespan in Drosophila. Here we describe a hitherto unknown transport system for citrate in mammalian cells. When liver and mammary epithelial cells were pretreated with the iron supplement ferric ammonium citrate (FAC), uptake of citrate increased >10-fold. Iron chelators abrogated the stimulation of citrate uptake in FAC-treated cells. The iron exporter ferroportin had no role in this process. The stimulation of citrate uptake also occurred when Fe3+ was added during uptake without pretreatment. Similarly, uptake of Fe3+ was enhanced by citrate. The Fe3+-citrate uptake was coupled to Na+. This transport system was detectable in primary hepatocytes and neuronal cell lines. The functional features of this citrate transport system distinguish it from NaCT. Loss-of-function mutations in NaCT cause early-onset epilepsy and encephalopathy; the newly discovered Na+-coupled Fe3+-citrate transport system might offer a novel treatment strategy for these patients to deliver citrate into affected neurons independent of NaCT. It also has implications to iron-overload conditions where circulating free iron increases, which would stimulate cellular uptake of citrate and consequently affect multiple metabolic pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells

Ogura

Babu

Miyauchi

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Obese individuals had higher hepcidin and lower TS levels (although not significantly), which may be consistent with low grade inflammation that is associated with a high BMI [ 27 , 28 , 29 , 30 ]. We have previously found significantly higher hepcidin levels in overweight male C282Y homozygotes indicating perhaps that hepcidin is up‐regulated in response to low grade inflammation, which may partly protect against the inadequate production of hepcidin (arising from the mutation in HFE) and thereby modulating phenotypic expression of HH [ 6 ]. The observation that a lower percentage of obese homozygotes had detectable NTBI is also in keeping with the lower TS noted in this cohort and a previously described decreased iron burden in overweight female C282Y homozygotes [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…In Ireland, 93% of individuals with hereditary haemochromatosis (HH) are homozygous for the C282Y mutation in the HFE gene [ 1 , 2 ]. C282Y homozygotes are deficient in the liver‐derived hormone hepcidin, leading to increased intestinal iron absorption and systemic iron overload [ 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…We have previously examined hepcidin and NTBI in a cohort comprising untreated non‐iron loaded and iron loaded C282Y homozygotes, compound heterozygotes (heterozygous for C282Y and H63D) and others with less at risk of iron overload genotypes. We found that C282Y homozygotes had significantly lower hepcidin levels and significantly higher NTBI levels compared to those with the ‘less at risk of iron overload’ genotypes [ 6 ]. We also reported a strong correlation of TS with NTBI [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…We found that C282Y homozygotes had significantly lower hepcidin levels and significantly higher NTBI levels compared to those with the ‘less at risk of iron overload’ genotypes [ 6 ]. We also reported a strong correlation of TS with NTBI [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

NTBI levels in C282Y homozygotes after therapeutic phlebotomy

Ryan

Mulready

Wiegerinck

et al. 2022

eJHaem

Self Cite

View full text Add to dashboard Cite

C282Y homozygotes exposed to sustained elevated transferrin saturation (TS) may develop worsening clinical symptoms. This might be related to the appearance of nontransferrin bound iron (NTBI) when TS≥50% and labile plasma iron (LPI) when TS levels reach 75-80%. In this study, NTBI levels were examined in 219 randomly selected untreated and treated C282Y homozygotes. Overall, 161 of 219 had TS ≥ 50%, 124 of whom had detectable NTBI (≥0.47 µM, 1.81 µM [0.92-2.46 µM]) with a median serum ferritin 320 µg/L (226-442 µg/L). Ninety of 219 homozygotes had TS ≥ 75%, and all had detectable NTBI (2.21 µM [1.53-2.59 µM] with a median ferritin 338 µg/L [230-447 µg/L]). Of 125 homozygotes who last had phlebotomy ≥12 months ago (42 months [25-74 months], 92 had TS levels ≥ 50%, and 70 of these had NTBI ≥ 0.47 µM (2.06 µM [1.23-2.61µM]). Twenty-six of these 70 had a normal ferritin. Fifty-five of 125 had TS ≥ 75%, and NTBI was detected in all of these (2.32 µM [1.57-2.77 µM]) with a median ferritin 344 µg/L (255-418 µg/L). Eighteen of these 55 had a normal ferritin. In summary, NTBI is frequently found in C282Y homozygotes with TS ≥ 50%. Furthermore, C282Y homozygotes in the maintenance phase often have TS ≥ 50% together with a normal ferritin. Therefore, monitoring the TS level during the maintenance phase is recommended as an accessible clinical marker of the presence of NTBI.

show abstract

Indices of iron homeostasis in asymptomatic subjects with HFE mutations and moderate ferritin elevation during iron removal treatment

Infanti

Leitner²,

Moe³

et al. 2022

Blood Cells, Molecules, and Diseases

View full text Add to dashboard Cite

Correlates of Hepcidin and NTBI according to <b><i>HFE</i></b> Status in Patients Referred to a Liver Centre

Cited by 8 publications

References 35 publications

RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells

RETRACTED ARTICLE: Identification of a novel Na+-coupled Fe3+-citrate transport system, distinct from mammalian INDY, for uptake of citrate in mammalian cells

NTBI levels in C282Y homozygotes after therapeutic phlebotomy

Indices of iron homeostasis in asymptomatic subjects with HFE mutations and moderate ferritin elevation during iron removal treatment

Contact Info

Product

Resources

About