Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian Randomization Study

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Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian Randomization Study. / Moen, Ingrid W.; Bergholdt, Helle K. M.; Mandrup-Poulsen, Thomas; Nordestgaard, Børge G.; Ellervik, Christina.

In: Clinical Chemistry, Vol. 64, No. 2, 2018, p. 374-385.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Moen, IW, Bergholdt, HKM, Mandrup-Poulsen, T, Nordestgaard, BG & Ellervik, C 2018, 'Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian Randomization Study', Clinical Chemistry, vol. 64, no. 2, pp. 374-385. https://doi.org/10.1373/clinchem.2017.276055

APA

Moen, I. W., Bergholdt, H. K. M., Mandrup-Poulsen, T., Nordestgaard, B. G., & Ellervik, C. (2018). Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian Randomization Study. Clinical Chemistry, 64(2), 374-385. https://doi.org/10.1373/clinchem.2017.276055

Vancouver

Moen IW, Bergholdt HKM, Mandrup-Poulsen T, Nordestgaard BG, Ellervik C. Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian Randomization Study. Clinical Chemistry. 2018;64(2):374-385. https://doi.org/10.1373/clinchem.2017.276055

Author

Moen, Ingrid W. ; Bergholdt, Helle K. M. ; Mandrup-Poulsen, Thomas ; Nordestgaard, Børge G. ; Ellervik, Christina. / Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian Randomization Study. In: Clinical Chemistry. 2018 ; Vol. 64, No. 2. pp. 374-385.

Bibtex

@article{6568aef1e0074b43abf073d8efc9cb15,
title = "Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian Randomization Study",
abstract = "BACKGROUND: It is unknown why increased plasma ferritin concentration predicts all-cause mortality. As low-grade inflammation and increased plasma ferritin concentration are associated with all-cause mortality, we hypothesized that increased plasma ferritin concentration is genetically associated with low-grade inflammation.METHODS: We investigated whether increased plasma ferritin concentration is associated with low-grade inflammation [i.e., increased concentrations of C-reactive protein (CRP) and complement component 3 (C3)] in 62537 individuals from the Danish general population. We also applied a Mendelian randomization approach, using the hemochromatosis genotype C282Y/C282Y as an instrument for increased plasma ferritin concentration, to assess causality.RESULTS: For a doubling in plasma ferritin concentration, the odds ratio (95% CI) for CRP ≥2 vs <2 mg/L was 1.12 (1.09-1.16), with a corresponding genetic estimate for C282Y/C282Y of 1.03 (1.01-1.06). For a doubling in plasma ferritin concentration, odds ratio (95% CI) for complement C3 >1.04 vs ≤1.04 g/L was 1.28 (1.21-1.35), and the corresponding genetic estimate for C282Y/C282Y was 1.06 (1.03-1.12). Mediation analyses showed that 74% (95% CI, 24-123) of the association of C282Y/C282Y with risk of increased CRP and 56% (17%-96%) of the association of C282Y/C282Y with risk of increased complement C3 were mediated through plasma ferritin concentration.CONCLUSIONS: Increased plasma ferritin concentration as a marker of increased iron concentration is associated observationally and genetically with low-grade inflammation, possibly indicating a causal relationship from increased ferritin to inflammation. However, as HFE may also play an immunological role indicating pleiotropy and as incomplete penetrance of C282Y/C282Y indicates buffering mechanisms, these weaknesses in the study design could bias the genetic estimates.",
keywords = "Journal Article",
author = "Moen, {Ingrid W.} and Bergholdt, {Helle K. M.} and Thomas Mandrup-Poulsen and Nordestgaard, {B{\o}rge G.} and Christina Ellervik",
note = "{\textcopyright} 2017 American Association for Clinical Chemistry.",
year = "2018",
doi = "10.1373/clinchem.2017.276055",
language = "English",
volume = "64",
pages = "374--385",
journal = "Clinical Chemistry",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry, Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Increased Plasma Ferritin Concentration and Low-Grade Inflammation-A Mendelian Randomization Study

AU - Moen, Ingrid W.

AU - Bergholdt, Helle K. M.

AU - Mandrup-Poulsen, Thomas

AU - Nordestgaard, Børge G.

AU - Ellervik, Christina

N1 - © 2017 American Association for Clinical Chemistry.

PY - 2018

Y1 - 2018

N2 - BACKGROUND: It is unknown why increased plasma ferritin concentration predicts all-cause mortality. As low-grade inflammation and increased plasma ferritin concentration are associated with all-cause mortality, we hypothesized that increased plasma ferritin concentration is genetically associated with low-grade inflammation.METHODS: We investigated whether increased plasma ferritin concentration is associated with low-grade inflammation [i.e., increased concentrations of C-reactive protein (CRP) and complement component 3 (C3)] in 62537 individuals from the Danish general population. We also applied a Mendelian randomization approach, using the hemochromatosis genotype C282Y/C282Y as an instrument for increased plasma ferritin concentration, to assess causality.RESULTS: For a doubling in plasma ferritin concentration, the odds ratio (95% CI) for CRP ≥2 vs <2 mg/L was 1.12 (1.09-1.16), with a corresponding genetic estimate for C282Y/C282Y of 1.03 (1.01-1.06). For a doubling in plasma ferritin concentration, odds ratio (95% CI) for complement C3 >1.04 vs ≤1.04 g/L was 1.28 (1.21-1.35), and the corresponding genetic estimate for C282Y/C282Y was 1.06 (1.03-1.12). Mediation analyses showed that 74% (95% CI, 24-123) of the association of C282Y/C282Y with risk of increased CRP and 56% (17%-96%) of the association of C282Y/C282Y with risk of increased complement C3 were mediated through plasma ferritin concentration.CONCLUSIONS: Increased plasma ferritin concentration as a marker of increased iron concentration is associated observationally and genetically with low-grade inflammation, possibly indicating a causal relationship from increased ferritin to inflammation. However, as HFE may also play an immunological role indicating pleiotropy and as incomplete penetrance of C282Y/C282Y indicates buffering mechanisms, these weaknesses in the study design could bias the genetic estimates.

AB - BACKGROUND: It is unknown why increased plasma ferritin concentration predicts all-cause mortality. As low-grade inflammation and increased plasma ferritin concentration are associated with all-cause mortality, we hypothesized that increased plasma ferritin concentration is genetically associated with low-grade inflammation.METHODS: We investigated whether increased plasma ferritin concentration is associated with low-grade inflammation [i.e., increased concentrations of C-reactive protein (CRP) and complement component 3 (C3)] in 62537 individuals from the Danish general population. We also applied a Mendelian randomization approach, using the hemochromatosis genotype C282Y/C282Y as an instrument for increased plasma ferritin concentration, to assess causality.RESULTS: For a doubling in plasma ferritin concentration, the odds ratio (95% CI) for CRP ≥2 vs <2 mg/L was 1.12 (1.09-1.16), with a corresponding genetic estimate for C282Y/C282Y of 1.03 (1.01-1.06). For a doubling in plasma ferritin concentration, odds ratio (95% CI) for complement C3 >1.04 vs ≤1.04 g/L was 1.28 (1.21-1.35), and the corresponding genetic estimate for C282Y/C282Y was 1.06 (1.03-1.12). Mediation analyses showed that 74% (95% CI, 24-123) of the association of C282Y/C282Y with risk of increased CRP and 56% (17%-96%) of the association of C282Y/C282Y with risk of increased complement C3 were mediated through plasma ferritin concentration.CONCLUSIONS: Increased plasma ferritin concentration as a marker of increased iron concentration is associated observationally and genetically with low-grade inflammation, possibly indicating a causal relationship from increased ferritin to inflammation. However, as HFE may also play an immunological role indicating pleiotropy and as incomplete penetrance of C282Y/C282Y indicates buffering mechanisms, these weaknesses in the study design could bias the genetic estimates.

KW - Journal Article

U2 - 10.1373/clinchem.2017.276055

DO - 10.1373/clinchem.2017.276055

M3 - Journal article

C2 - 29038157

VL - 64

SP - 374

EP - 385

JO - Clinical Chemistry

JF - Clinical Chemistry

SN - 0009-9147

IS - 2

ER -

ID: 189626074