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Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y

BACKGROUND: Screening program participants with iron overload (IO) phenotypes without HFE p.C282Y/p.C282Y are incompletely characterized. METHODS: We studied white participants who had IO phenotypes without p.C282Y/p.C282Y in post-screening clinical examinations (CE). We defined IO phenotypes as a)...

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Autores principales: Barton, James C., Barton, J. Clayborn, Acton, Ronald T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328571/
https://www.ncbi.nlm.nih.gov/pubmed/35895739
http://dx.doi.org/10.1371/journal.pone.0271973
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author Barton, James C.
Barton, J. Clayborn
Acton, Ronald T.
author_facet Barton, James C.
Barton, J. Clayborn
Acton, Ronald T.
author_sort Barton, James C.
collection PubMed
description BACKGROUND: Screening program participants with iron overload (IO) phenotypes without HFE p.C282Y/p.C282Y are incompletely characterized. METHODS: We studied white participants who had IO phenotypes without p.C282Y/p.C282Y in post-screening clinical examinations (CE). We defined IO phenotypes as a) elevated serum ferritin (SF) and transferrin saturation (TS) at screening and CE, and b) absence of IO treatment, anemia, transfusion >10 units, alcohol intake >30 g/d, hepatitis B or C, and pregnancy. We defined IO-related disease as elevated alanine or aspartate aminotransferase (ALT/AST) or swelling/tenderness of 2nd/3rd metacarpophalangeal (MCP) joints. All participants had HFE p.C282Y and p.H63D genotyping. RESULTS: There were 32 men and 26 women (mean age 54±16 y). Median food/supplemental iron intakes were 14.3/0.0 mg/d. Relative risks of HFE genotypes were 12.9 (p.C282Y/p.H63D), 3.0 (p.H63D/p.H63D), 1.9 (p.C282Y/wt), 0.9 (p.H63D/wt), and 0.5 (wt/wt) compared to 42,640 white screening participants without IO phenotypes or p.C282Y/p.C282Y. Regression on SF revealed positive associations: MCV (p = 0.0006; β coefficient = 0.4531); swelling/tenderness of MCP joints (p = 0.0033; β = 0.3455); and p.H63D/wt (p = 0.0015; β = 0.4146). IO-related disease (18 elevated ALT/AST, one swelling/tenderness of MCP joints) occurred in 19 participants (7 men, 12 women). Median MCV was higher in participants with IO-related disease (97 fL vs. 94 fL; p = 0.0007). Logistic regression on IO-related disease revealed a significant association with diabetes (p = 0.0416; odds ratio 18.9 (95% confidence interval 1.0, 341.1)). CONCLUSIONS: In the present 58 screening program participants who had IO phenotypes without HFE p.C282Y/p.C282Y, relative risks of HFE genotypes p.C282Y/p.H63D, p.H63D/p.H63D, and p.C282Y/wt were significantly higher than in 42,640 white screening participants with neither IO phenotypes nor p.C282Y/p.C282Y. SF was significantly associated with MCV, swelling/tenderness of 2nd/3rd MCP joints, and p.H63D/wt. IO-related disease was significantly associated with MCV and diabetes.
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spelling pubmed-93285712022-07-28 Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y Barton, James C. Barton, J. Clayborn Acton, Ronald T. PLoS One Research Article BACKGROUND: Screening program participants with iron overload (IO) phenotypes without HFE p.C282Y/p.C282Y are incompletely characterized. METHODS: We studied white participants who had IO phenotypes without p.C282Y/p.C282Y in post-screening clinical examinations (CE). We defined IO phenotypes as a) elevated serum ferritin (SF) and transferrin saturation (TS) at screening and CE, and b) absence of IO treatment, anemia, transfusion >10 units, alcohol intake >30 g/d, hepatitis B or C, and pregnancy. We defined IO-related disease as elevated alanine or aspartate aminotransferase (ALT/AST) or swelling/tenderness of 2nd/3rd metacarpophalangeal (MCP) joints. All participants had HFE p.C282Y and p.H63D genotyping. RESULTS: There were 32 men and 26 women (mean age 54±16 y). Median food/supplemental iron intakes were 14.3/0.0 mg/d. Relative risks of HFE genotypes were 12.9 (p.C282Y/p.H63D), 3.0 (p.H63D/p.H63D), 1.9 (p.C282Y/wt), 0.9 (p.H63D/wt), and 0.5 (wt/wt) compared to 42,640 white screening participants without IO phenotypes or p.C282Y/p.C282Y. Regression on SF revealed positive associations: MCV (p = 0.0006; β coefficient = 0.4531); swelling/tenderness of MCP joints (p = 0.0033; β = 0.3455); and p.H63D/wt (p = 0.0015; β = 0.4146). IO-related disease (18 elevated ALT/AST, one swelling/tenderness of MCP joints) occurred in 19 participants (7 men, 12 women). Median MCV was higher in participants with IO-related disease (97 fL vs. 94 fL; p = 0.0007). Logistic regression on IO-related disease revealed a significant association with diabetes (p = 0.0416; odds ratio 18.9 (95% confidence interval 1.0, 341.1)). CONCLUSIONS: In the present 58 screening program participants who had IO phenotypes without HFE p.C282Y/p.C282Y, relative risks of HFE genotypes p.C282Y/p.H63D, p.H63D/p.H63D, and p.C282Y/wt were significantly higher than in 42,640 white screening participants with neither IO phenotypes nor p.C282Y/p.C282Y. SF was significantly associated with MCV, swelling/tenderness of 2nd/3rd MCP joints, and p.H63D/wt. IO-related disease was significantly associated with MCV and diabetes. Public Library of Science 2022-07-27 /pmc/articles/PMC9328571/ /pubmed/35895739 http://dx.doi.org/10.1371/journal.pone.0271973 Text en © 2022 Barton et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Barton, James C.
Barton, J. Clayborn
Acton, Ronald T.
Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y
title Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y
title_full Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y
title_fullStr Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y
title_full_unstemmed Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y
title_short Iron overload phenotypes and HFE genotypes in white hemochromatosis and iron overload screening study participants without HFE p.C282Y/p.C282Y
title_sort iron overload phenotypes and hfe genotypes in white hemochromatosis and iron overload screening study participants without hfe p.c282y/p.c282y
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328571/
https://www.ncbi.nlm.nih.gov/pubmed/35895739
http://dx.doi.org/10.1371/journal.pone.0271973
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