Genetic factors influencing ferritin levels in 14,126 blood donors: results from the Danish Blood Donor Study

Sørensen, Erik; Rigas, Andreas S.; Thørner, Lise Wegner; Burgdorf, Kristoffer Sølvsten; Pedersen, Ole Birger; Petersen, Mikkel Steen; Hjalgrim, Henrik; Erikstrup, Christian; Ullum, Henrik

doi:10.1111/trf.13397

Cited by 21 publications

(29 citation statements)

References 22 publications

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“…Nevertheless, the frequency of the A736V was similar in first‐time and high‐intensity groups, and it had no observed association with hemoglobin or ferritin within high‐intensity donors in longitudinal models. The variable effects of A736V among first‐time and high‐intensity donors may explain why it did not impact ferritin in women in a large cohort of donors with a range of donation intensity and is consistent with its variable association with hemoglobin and ferritin found in other studies …”

Section: Discussionsupporting

confidence: 88%

“…11,12 There is evidence for higher hemoglobin or ferritin in blood donors with H63D and C282Y, but the findings sometimes vary by sex and number of mutated alleles. [8][9][10]12 Here, we found that H63D was more strongly associated with increased ferritin and hemoglobin in high-intensity donors than C282Y. This was somewhat surprising, since C282Y is more strongly associated with hemochromatosis.…”

Section: Discussionmentioning

confidence: 56%

“…Several studies have examined the association of genetic factors with iron deficiency and anemia in blood donors. [9][10][11][12] Hepcidin decreases iron absorption from the gastrointestinal tract, 13 and genetic modifiers of its production may influence iron recovery following blood donation. 6 The HFE C282Y (rs1800562) and H63D (rs1799945) mutations decrease hepcidin production and increase risk for hemochromatosis.…”

Section: Conclusion: Behavioral and Genetic Modifiersmentioning

confidence: 99%

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Genetic and behavioral modification of hemoglobin and iron status among first‐time and high‐intensity blood donors

et al. 2020

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BACKGROUND Some people rapidly develop iron deficiency anemia following blood donation, while others can repeatedly donate without becoming anemic. METHODS Two cohorts of blood donors were studied. Participants (775) selected from a 2‐year longitudinal study were classified into six analysis groups based on sex, donation intensity, and low hemoglobin deferral. Associations with iron supplement use, cigarette smoking, and four genetic variants of iron metabolism were examined at enrollment and with longitudinal regression models. An unbiased assessment of genetic variability and ability to repeatedly donate blood without experiencing low hemoglobin deferral was conducted on participants (13,403) in a cross‐sectional study who were examined by genome wide association (GWA). RESULTS Behaviors and genetic variants were associated with differences in hemoglobin and ferritin change following repeated donation. At least weekly iron supplement use was associated with improved status in first‐time donors, while daily use was associated with improved status in high‐intensity donors. Cigarette smoking was associated with 0.5 g/dL increased hemoglobin in high‐intensity donors. A736V in TMPRSS6 was associated with a rapid drop in hemoglobin and ferritin in first‐time females following repeated donation. Conversely, the protective TMPRSS6 genotype was not enriched among high‐intensity donors. H63D in HFE was associated with increased hemoglobin in female high‐intensity donors. However, no differences in genotype between first‐time and high‐intensity donors were found in GWA analyses. CONCLUSION Behavioral and genetic modifiers contributed to first‐time donor hemoglobin and iron status, while iron supplement use was more important than underlying genetics in high‐intensity donors.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 56%

Section: Conclusion: Behavioral and Genetic Modifiersmentioning

confidence: 99%

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Genetic and behavioral modification of hemoglobin and iron status among first‐time and high‐intensity blood donors

et al. 2020

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“…Studies of blood donors have strengthened the hypothesis that genetic variants of iron genes, especially TMPRSS6 and HFE, reported to influence iron parameters 49,50 and hepcidin, 51 may predispose to or protect individuals from iron deficiency. 52 In a novel murine model, genetic iron deficiency anemia was caused by loss of the enzyme of the sulfur assimilation pathway bisphosphate-39-nucleotidase (Bpnt1). Iron deficiency anemia characterizes both germinal and intestinal conditional Bpnt1 knockout mice, establishing a novel link between sulfur and iron homeostasis.…”

Section: Genetics Of Iron Deficiencymentioning

confidence: 99%

Iron deficiency

Camaschella¹

2019

Blood

473

415

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Iron deficiency anemia affects >1.2 billions individuals worldwide, and iron deficiency in the absence of anemia is even more frequent. Total-body (absolute) iron deficiency is caused by physiologically increased iron requirements in children, adolescents, young and pregnant women, by reduced iron intake, or by pathological defective absorption or chronic blood loss. Adaptation to iron deficiency at the tissue level is controlled by iron regulatory proteins to increase iron uptake and retention; at the systemic level, suppression of the iron hormone hepcidin increases iron release to plasma by absorptive enterocytes and recycling macrophages. The diagnosis of absolute iron deficiency is easy unless the condition is masked by inflammatory conditions. All cases of iron deficiency should be assessed for treatment and underlying cause. Special attention is needed in areas endemic for malaria and other infections to avoid worsening of infection by iron treatment. Ongoing efforts aim at optimizing iron salts–based therapy by protocols of administration based on the physiology of hepcidin control and reducing the common adverse effects of oral iron. IV iron, especially last-generation compounds administered at high doses in single infusions, is becoming an effective alternative in an increasing number of conditions because of a more rapid and persistent hematological response and acceptable safety profile. Risks/benefits of the different treatments should be weighed in a personalized therapeutic approach to iron deficiency.

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“…The Danish Donor Cohort recently added specific consent for collection, retention, and testing of DNA and plasma samples from a subset of blood donors in Denmark. 27 This study is in the process of generating GWAS and other laboratory data to allow analyses of donor genetic and biological factors that may impact downstream donor health and transfusion efficacy and complications. However, they have not acquired and stored samples of RBCs for evaluation of storage hemolysis parameters.…”

Section: Discussionmentioning

confidence: 99%

Blood, sweat, and tears: Red Blood Cell‐Omics study objectives, design, and recruitment activities

et al. 2018

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BACKGROUND: The Red Blood Cell (RBC)-Omics study was initiated to build a large data set containing behavioral, genetic, and biochemical characteristics of blood donors with linkage to outcomes of the patients transfused with their donated RBCs. STUDY DESIGN AND METHODS: The cohort was recruited from four US blood centers. Demographic and donation data were obtained from center records. A questionnaire to assess pica, restless leg syndrome, iron supplementation, hormone use, and menstrual and pregnancy history was completed at enrollment. Blood was obtained for a complete blood count, DNA, and ferritin testing. A leukocyte-reduced RBC sample was transferred to a custom storage bag for hemolysis testing at Storage Days 39 to 42. A subset was recalled to evaluate the kinetics and stability of hemolysis measures. RESULTS: A total of 13,403 racially/ethnically diverse (12% African American, 12% Asian, 8% Hispanic, 64% white, and 5% multiracial/other) donors of both sexes were enrolled and ranged from 18 to 90 years of age; 15% were high-intensity donors (nine or more donations in the prior 24 mo without low hemoglobin deferral). Data elements are available for 97% to 99% of the cohort. CONCLUSIONS: The cohort provides demographic, behavioral, biochemical, and genetic data for a broad range of blood donor studies related to iron metabolism, adverse consequences of iron deficiency, and differential hemolysis (including oxidative and osmotic stress perturbations) during RBC storage. Linkage to recipient outcomes may permit analysis of how donor characteristics affect transfusion efficacy. Repository DNA, plasma, and RBC samples should expand the usefulness of the current data set.

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Genetic factors influencing ferritin levels in 14,126 blood donors: results from the Danish Blood Donor Study

Abstract: Genetic variants associated with hemochromatosis may protect donors against depleted iron stores. In addition, we showed that presence of the T-allele at rs855791 in TMPRSS6 was associated with lower iron stores in men.

Cited by 21 publications

References 22 publications

Genetic and behavioral modification of hemoglobin and iron status among first‐time and high‐intensity blood donors

Genetic and behavioral modification of hemoglobin and iron status among first‐time and high‐intensity blood donors

Iron deficiency

Blood, sweat, and tears: Red Blood Cell‐Omics study objectives, design, and recruitment activities

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