Serum ferritin concentration is affected by ferroportin Q248H mutation in Africans

Kasvosve, Ishmael; Tshwenyego, Uyapo; Phuthego, Thato; Koto, Garesego; Zachariah, Matshediso; Nyepetsi, Naledi Gape; Motswaledi, Modisa S.

doi:10.1016/j.cca.2015.02.037

Cited by 12 publications

(4 citation statements)

References 21 publications

(27 reference statements)

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“…We further hypothesized that reduced hepcidin-induced degradation of FPN among Q248H carriers might lead to improved iron absorption by duodenal enterocytes and iron recycling by macrophages. Consistent with this hypothesis, we observed a trend toward improved iron status among children carrying the mutation corroborating findings from other studies ( 15 – 18 ). Zinc protoporphyrin levels were also significantly lower among Q248H individuals, suggesting no evidence for iron-deficient erythropoiesis, as previously suggested ( 3 ).…”

Section: Discussionsupporting

confidence: 92%

The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia

et al. 2019

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Iron acquisition is critical for life. Ferroportin (FPN) exports iron from mature erythrocytes, and deletion of the Fpn gene results in hemolytic anemia and increased fatality in malaria-infected mice. The FPN Q248H mutation (glutamine to histidine at position 248) renders FPN partially resistant to hepcidin-induced degradation and was associated with protection from malaria in human studies of limited size. Using data from cohorts including over 18,000 African children, we show that the Q248H mutation is associated with modest protection against anemia, hemolysis, and iron deficiency, but we found little evidence of protection against severe malaria or bacteremia. We additionally observed no excess Plasmodium growth in Q248H erythrocytes ex vivo, nor evidence of selection driven by malaria exposure, suggesting that the Q248H mutation does not protect from malaria and is unlikely to deprive malaria parasites of iron essential for their growth.

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Section: Discussionsupporting

confidence: 92%

The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia

et al. 2019

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“…The ferroportin variant Q248H is common (a few %) in populations of African ancestry and has been weakly associated with increased serum ferritin (Gordeuk et al, 2003; Kasvosve et al, 2015; Rivers et al, 2007). The polymorphism may confer a somewhat decreased sensitivity of ferroportin to hepcidin, perhaps because of its proximity to cytoplasmic ubiquitination sites involved in hepcidin-induced ferroportin endocytosis (Nekhai et al, 2013).…”

Section: Genetic Disorders Of Ferroportin and Their Effects On Systemmentioning

confidence: 99%

Ironing out Ferroportin

2015

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Maintaining physiologic iron concentrations in tissues is critical for metabolism and host defense. Iron absorption in the duodenum, recycling of iron from senescent erythrocytes, and iron mobilization from storage in macrophages and hepatocytes constitute the major iron flows into plasma for distribution to tissues, predominantly for erythropoiesis. All iron transfer to plasma occurs through the iron exporter ferroportin. The concentration of functional membrane-associated ferroportin is controlled by its ligand, the iron-regulatory hormone hepcidin, and fine-tuned by regulatory mechanisms serving iron homeostasis, oxygen utilization, host defense and erythropoiesis. Fundamental questions about the structure and biology of ferroportin remain to be answered.

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“…The ferroportin (Q248H) rs11568350 variant has the substitution of glutamine with histidine at position 248 (Q248H) in exon 6. In an African study, the ferroportin variant was seen as prudent protection against iron deficiency anemia [ 20 ]. The functional significance of the missense variant transferrin (G258S) (Gly) > (Ser) rs602662 polymorphism is still unclear [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Gene Variants in the Iron Metabolism of Anemic Adolescent Girls

Varikuti¹,

Parasannavar²,

Hemalatha³

et al. 2021

Cureus

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Background and objectives Iron deficiency anemia (IDA) and the role of genetic variants in determining the iron status in adolescent girls are not yet well-understood. This study aims to investigate the association of the rs602662, rs1049296, rs1805051, rs855791, rs224589, and rs11568350 genes with IDA and iron bio-status parameters. Methods This study consisted of 132 patients (IDA group) and 110 healthy controls. The genotype was analyzed through polymerase chain reaction-restriction fragment length polymorphism. Results No differences were noted in the distribution of genotype and allele frequency single nucleotide polymorphism between the IDA and control group. In the IDA group, the GA carriers of rs602662 had a higher hemoglobin concentration (P=0.02) and packed cell volume (P=0.007), whereas transferrin saturation was increased in AA (P=0.02). The genetic variants rs1049296, rs1805051, rs224589, and rs855791 had a non-statistical significance on hematological parameters. Both the GT and TT carriers of the rs11568350 gene showed a low hemoglobin concentration (P=0.02 and <0.001) and mean corpuscular hemoglobin in GT carrier (P=0.01), whereas the TT risk of this gene showed a decreased packed cell volume (P=0.01). In the control patients, no association was observed with serum iron and hematological parameters. Conclusion Of these genetic variants, the GG and GA genotype frequency in rs602662 and the GG, GT, and TT in rs11568350 were associated with low iron status in anemic patients compared to the control patients.

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Serum ferritin concentration is affected by ferroportin Q248H mutation in Africans

Cited by 12 publications

References 21 publications

The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia

The ferroportin Q248H mutation protects from anemia, but not malaria or bacteremia

Ironing out Ferroportin

The Role of Gene Variants in the Iron Metabolism of Anemic Adolescent Girls

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