Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene☆

Gordeuk, Victor R.; Caleffi, Angela; Corradini, Elena; Ferrara, Francesca; Jones, R.; Castro, Oswaldo; Onyekwere, Onyinye; Kittles, Rick A.; Pignatti, Elisa; Montosi, Giuliana; Garuti, Cinzia; Gangaidzo, Innocent T.; Gomo, Zvenyika A. R.; Moyo, Victor; Rouault, Tracey A.; MacPhail, Patrick; Pietrangelo, Antonello

doi:10.1016/s1079-9796(03)00164-5

Cited by 191 publications

(118 citation statements)

References 14 publications

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“…This is consistent with our hypothesis that SF is positively associated with Q248H, and with previous reports [2,3]. Further, the occurrence of Q248H in AA could partly explain the higher mean SF levels typically observed in AA than in whites [1-3].…”

Section: Discussionsupporting

confidence: 93%

“…However, the possible role of Q248H in the causation of increased serum ferritin concentration (SF) or iron overload in sub-Saharan African Natives or AA is incompletely defined. Among 22 southern African first-degree family members, 10 of whom were Q248H heterozygotes, Q248H was associated with a trend of higher SF to aspartate aminotransferase ratios [3]. In 278 AA males and 293 AA females from a southern California screening program who lacked HFE C282Y, the mean SF of 26 Q248H heterozygotes did not differ significantly from that of wild-type homozygotes [2].…”

Section: Introductionmentioning

confidence: 87%

“…The ferroportin (FPN1) Q248H polymorphism (cDNA 744 G→T [Gln248His, Q248H]) occurs in sub-Saharan African Natives and in African Americans (AA) with and without iron overload [1][2][3]. However, the possible role of Q248H in the causation of increased serum ferritin concentration (SF) or iron overload in sub-Saharan African Natives or AA is incompletely defined.…”

Section: Introductionmentioning

confidence: 99%

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Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Rivers

Barton²,

Gordeuk

et al. 2007

Blood Cells, Molecules, and Diseases

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The ferroportin (FPN1) Q248H polymorphism has been associated with increased serum ferritin (SF) levels in sub-Saharan Africans and in African Americans (AA). AA participants of the HEIRS Study who did not have HFE C282Y or H63D who had elevated initial screening SF (≥300 μg/L in men and ≥200 μg/L in women) (defined as cases) were frequency-matched to AA participants with normal SF (defined as controls) to investigate the association of the Q248H with elevated SF. 10.4% of cases and 6.7% of controls were Q248H heterozygotes (P = 0.257). Q248H homozygosity was observed in 0.5% of the cases and none of the controls. The frequency of Q248H was higher among men with elevated SF than among control men (P = 0.047); corresponding differences were not observed among women. This appeared to be unrelated to selfCorrespondence: Dr. James C. Barton G105, 2022 Brookwood Medical Center Drive Birmingham, AL 35209 Telephone 205-877-2888 FAX 205-877-2039 ironmd@dnamail.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. reports of a previous diagnosis of liver disease. Men with elevated SF were three times more likely than women with elevated SF to have Q248H (P = 0.012). There were no significant differences in Q248H frequencies in men and women control participants. We conclude that the frequency of the FPN1 Q248H polymorphism is greater in AA men with elevated SF than in those with normal SF. NIH Public Access

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Rivers

Barton²,

Gordeuk

et al. 2007

Blood Cells, Molecules, and Diseases

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“…It is expected that new genes and variants that influence Fe stores will be found in the near future. Since the preparation of this paper, a gene responsible for 1q-linked juvenile haemochromatosis has been proposed and named HFE2, and a causal mutation identified (Papanikoloau et al 2004), while a new mutation (Q248H) in IREG1 has been found to be associated with iron overload in Africans and African-Americans Gordeuk et al 2003). …”

Section: Discussionmentioning

confidence: 99%

Of mice and men: genetic determinants of iron status

2004

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Fe homeostasis is maintained by regulation of Fe absorption to balance largely unregulated body Fe losses. The majority of human subjects maintain relatively constant Fe stores; however, Fe deficiency and Fe overload are common conditions. Fe overload is frequently associated with mutations in genes of Fe metabolism. The present paper summarises present knowledge of these mutations as well as indicating other genes that animal studies have implicated as candidates for influencing body Fe stores.

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“…3,8,10,11 Deletion of this amino acid causes loss of function and when studied in vitro causes accumulation of iron in cultured cells. 12 FPN1 is a putative transmembrane iron channel implicated in the egress of iron from duodenal enterocytes, macrophages, hepatocytes, and placenta (reviewed in McKie and Barlow 13 ).…”

mentioning

confidence: 99%

Primary iron overload with inappropriate hepcidin expression in V162del ferroportin disease

et al. 2005

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Ferroportin disease (hemochromatosis type 4) is a recently recognized disorder of human iron metabolism, characterized by iron deposition in macrophages, including Kupffer cells. Mutations in the gene encoding ferroportin 1, a cellular iron exporter, are responsible for this iron storage disease, inherited as an autosomal dominant trait. We present clinical, histopathological, and radiological findings in a family with the most common ferroportin mutation, V162del. In the index case, the disorder is characterized by abundant deposition of hemosiderin in all tissues investigated (mesenteric lymph node, liver, gastric and duodenal mucosa, and also in squamous cell carcinoma of the lung). The radiological findings indicated the presence of excess iron in bone marrow and spleen. Despite a significant burden of iron, no features of chronic liver disease were found in affected members of the family, including individuals aged up to 80 years. Hyperferritinemia greater than 1,000 g/L was a penetrant biochemical finding before the second decade in life and was associated with significantly increased serum concentrations of pro-hepcidin that correlated positively with urinary hepcidin concentrations. In conclusion, the systemic iron burden in ferroportin disease is not a sufficient cause for chronic liver disease. In patients with most, but not all, ferroportin mutations, retention of iron in macrophages of the liver and other organs may protect against damage to parenchymal cells. Finally, macrophage iron storage in ferroportin disease is associated with elevated serum pro-hepcidin levels. (HEPATOLOGY 2005;42:466-472.)

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Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene☆

Cited by 191 publications

References 14 publications

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

Of mice and men: genetic determinants of iron status

Primary iron overload with inappropriate hepcidin expression in V162del ferroportin disease

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