Iron, hemochromatosis genotypes, and risk of infections: a cohort study of 142 188 general population individuals
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Haemochromatosis C282Y homozygotes had increased risk of any infection, and markedly increased risk of sepsis and death from infections
C282Y homozygotes with normal iron, transferrin saturation, or ferritin, not currently recommended for genotyping, had high infection risk
It is unclear whether risk of infection is increased in individuals with hereditary haemochromatosis and in individuals with low or high plasma iron, transferrin saturation, or ferritin. Therefore, we tested whether high and low iron, transferrin saturation, and ferritin are associated with risk of infections observationally and genetically through HFE genotypes. We studied 142,188 Danish general population individuals. Iron, transferrin saturation, and ferritin were measured in 136,656, 136,599, and 38,020 individuals, respectively. HFE was genotyped for C282Y and H63D in 132,542 individuals. Median follow-up after study enrolment was 8 years(range:0-38years) for hospital and emergency room admissions with infections(n=20,394 individuals) using the National Patient Register, covering all Danish hospitals. Hazard ratios for any infection were 1.20(95%CI:1.12-1.28) and 1.14(1.07-1.22) in individuals with plasma iron≤5th or ≥95th percentile compared to individuals with iron from 26th-74th percentiles. Findings for transferrin saturation were similar, while infection risk was not increased in individuals with ferritin≤5th or ≥95th percentile. Hazard ratios in C282Y homozygotes versus non-carriers were 1.40(1.16-1.68) for any infection, 1.69(1.05-2.73) for sepsis, and 2.34(1.41-3.90) for death from infectious disease. Risk of infection was increased in C282Y homozygotes with normal plasma iron, transferrin saturation, or ferritin, and in C282Y homozygotes without liver disease, diabetes, and/or heart failure. In summary, low and high plasma iron and transferrin saturation were independently associated with increased infection risk. C282Y homozygotes had increased risk of any infection, sepsis, and death from infections. Even C282Y homozygotes with normal iron, transferrin saturation, or ferritin, not currently recommended for genotyping, had increased infection risk.
Originalsprog | Engelsk |
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Tidsskrift | Blood |
Vol/bind | 144 |
Udgave nummer | 7 |
Sider (fra-til) | 693-707 |
ISSN | 0006-4971 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
This study was conducted using data from the Copenhagen City Heart Study, the Copenhagen General Population Study, and the Danish General Suburban Population Study. The authors thank all participants and staff of the studies. The authors also thank J\u00F8rgen Kurtzhals from the University of Copenhagen for his invaluable assistance in obtaining essential microbiology data for this study. Furthermore, the authors express their gratitude to the 3 anonymous reviewers for their helpful and constructive suggestions during the review process. This work was supported by research grants from the Capital Region of Denmark, Karla og Verner S\u00F8rensens Almennyttige Fond, Beckett-Fonden, and the Independent Research Fund Denmark. The Copenhagen General Population Study and the Copenhagen City Heart Study are supported by the Danish Heart Foundation and Copenhagen University Hospital \u2013 Herlev and Gentofte. C.E. is partly funded by the Laboratory Medicine Endowment Fund of Boston Children's Hospital. Contribution: M.M. A.G. and J.H. conceived and designed the study; M.M. B.G.N. C.E. S.E.B. and J.H. collected the data and assembled the databases; M.M. A.G. B.G.N. C.E. J.P. S.E.B. and J.H. analyzed and interpreted the data; M.M. and J.H. wrote the manuscript drafts; M.M. A.G. B.G.N. C.E. J.P. S.E.B. and J.H. performed manuscript revision, had full access to all data, and approved the final manuscript; and M.M. and J.H. accessed and verified the underlying data reported in the manuscript.
Funding Information:
This work was supported by research grants from the Capital Region of Denmark, Karla og Verner S\u00F8rensens Almennyttige Fond, Beckett-Fonden, and the Independent Research Fund Denmark. The Copenhagen General Population Study and the Copenhagen City Heart Study are supported by the Danish Heart Foundation and Copenhagen University Hospital-Herlev and Gentofte. C.E. is partly funded by the Laboratory Medicine Endowment Fund of Boston Children\u2019s Hospital.
Publisher Copyright:
© 2024 American Society of Hematology
ID: 396988623