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

Erik Sørensen; Andreas S Rigas; Lise Wegner Thørner; Kristoffer Solvsten Burgdorf; Ole Birger Vesterager Pedersen; Mikkel S Petersen; Henrik Hjalgrim; Christian Erikstrup; Henrik Ullum

doi:10.1111/trf.13397

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

Erik Sørensen, Andreas S Rigas, Lise Wegner Thørner, Kristoffer Solvsten Burgdorf, Ole Birger Vesterager Pedersen, Mikkel S Petersen, Henrik Hjalgrim, Christian Erikstrup, Henrik Ullum

Department of Clinical Medicine

15 Citations (Scopus)

Abstract

BACKGROUND Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. STUDY DESIGN AND METHODS The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain containing protein gene (BTBD9 - associated with restless legs syndrome; rs9357271); and in the Transferrin gene (TF; rs2280673 and rs1830084). Multiple linear and logistic regression analyses were used to evaluate the effect of each SNP on ferritin levels and the risk of iron deficiency (ferritin < 15 ng/mL). RESULTS In HFE, the G-allele of rs1800562 was associated with lower iron stores in both sexes. This was also true for the C-allele of rs179945, but in men only. Also, the T-allele of TMPRSS6 rs855791 was negatively associated with iron stores in men. Homozygocity for C in rs1799945 was associated with iron deficiency in women. Results for all other genetic variants were insignificant. CONCLUSION 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.

Original language	English
Journal	Transfusion
Volume	56
Issue number	3
Pages (from-to)	622-627
Number of pages	6
ISSN	0041-1132
DOIs	https://doi.org/10.1111/trf.13397
Publication status	Published - 1 Mar 2016

Keywords

Adolescent
Adult
Aged
Anemia, Iron-Deficiency
Blood Donors
Female
Ferritins
Genetic Predisposition to Disease
Hemochromatosis Protein
Histocompatibility Antigens Class I
Humans
Logistic Models
Male
Membrane Proteins
Middle Aged
Polymorphism, Single Nucleotide
Serine Endopeptidases
Transcription Factors
Transferrin
Young Adult
Journal Article

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10.1111/trf.13397

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@article{d52cfaa436384912bad70645736081dc,

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

abstract = "BACKGROUND Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. STUDY DESIGN AND METHODS The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain containing protein gene (BTBD9 - associated with restless legs syndrome; rs9357271); and in the Transferrin gene (TF; rs2280673 and rs1830084). Multiple linear and logistic regression analyses were used to evaluate the effect of each SNP on ferritin levels and the risk of iron deficiency (ferritin < 15 ng/mL). RESULTS In HFE, the G-allele of rs1800562 was associated with lower iron stores in both sexes. This was also true for the C-allele of rs179945, but in men only. Also, the T-allele of TMPRSS6 rs855791 was negatively associated with iron stores in men. Homozygocity for C in rs1799945 was associated with iron deficiency in women. Results for all other genetic variants were insignificant. CONCLUSION 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.",

keywords = "Adolescent, Adult, Aged, Anemia, Iron-Deficiency, Blood Donors, Female, Ferritins, Genetic Predisposition to Disease, Hemochromatosis Protein, Histocompatibility Antigens Class I, Humans, Logistic Models, Male, Membrane Proteins, Middle Aged, Polymorphism, Single Nucleotide, Serine Endopeptidases, Transcription Factors, Transferrin, Young Adult, Journal Article",

author = "Erik S{\o}rensen and Rigas, {Andreas S} and Th{\o}rner, {Lise Wegner} and Burgdorf, {Kristoffer Solvsten} and Pedersen, {Ole Birger Vesterager} and Petersen, {Mikkel S} and Henrik Hjalgrim and Christian Erikstrup and Henrik Ullum",

note = "{\textcopyright} 2015 AABB.",

year = "2016",

month = mar,

day = "1",

doi = "10.1111/trf.13397",

language = "English",

volume = "56",

pages = "622--627",

journal = "Transfusion",

issn = "0041-1132",

publisher = "Wiley-Blackwell",

number = "3",

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TY - JOUR

T1 - Genetic factors influencing ferritin levels in 14,126 blood donors

T2 - results from the Danish Blood Donor Study

AU - Sørensen, Erik

AU - Rigas, Andreas S

AU - Thørner, Lise Wegner

AU - Burgdorf, Kristoffer Solvsten

AU - Pedersen, Ole Birger Vesterager

AU - Petersen, Mikkel S

AU - Hjalgrim, Henrik

AU - Erikstrup, Christian

AU - Ullum, Henrik

PY - 2016/3/1

Y1 - 2016/3/1

N2 - BACKGROUND Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. STUDY DESIGN AND METHODS The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain containing protein gene (BTBD9 - associated with restless legs syndrome; rs9357271); and in the Transferrin gene (TF; rs2280673 and rs1830084). Multiple linear and logistic regression analyses were used to evaluate the effect of each SNP on ferritin levels and the risk of iron deficiency (ferritin < 15 ng/mL). RESULTS In HFE, the G-allele of rs1800562 was associated with lower iron stores in both sexes. This was also true for the C-allele of rs179945, but in men only. Also, the T-allele of TMPRSS6 rs855791 was negatively associated with iron stores in men. Homozygocity for C in rs1799945 was associated with iron deficiency in women. Results for all other genetic variants were insignificant. CONCLUSION 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.

AB - BACKGROUND Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. STUDY DESIGN AND METHODS The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain containing protein gene (BTBD9 - associated with restless legs syndrome; rs9357271); and in the Transferrin gene (TF; rs2280673 and rs1830084). Multiple linear and logistic regression analyses were used to evaluate the effect of each SNP on ferritin levels and the risk of iron deficiency (ferritin < 15 ng/mL). RESULTS In HFE, the G-allele of rs1800562 was associated with lower iron stores in both sexes. This was also true for the C-allele of rs179945, but in men only. Also, the T-allele of TMPRSS6 rs855791 was negatively associated with iron stores in men. Homozygocity for C in rs1799945 was associated with iron deficiency in women. Results for all other genetic variants were insignificant. CONCLUSION 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Anemia, Iron-Deficiency

KW - Blood Donors

KW - Female

KW - Ferritins

KW - Genetic Predisposition to Disease

KW - Hemochromatosis Protein

KW - Histocompatibility Antigens Class I

KW - Humans

KW - Logistic Models

KW - Male

KW - Membrane Proteins

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Serine Endopeptidases

KW - Transcription Factors

KW - Transferrin

KW - Young Adult

KW - Journal Article

U2 - 10.1111/trf.13397

DO - 10.1111/trf.13397

M3 - Journal article

C2 - 26597663

SN - 0041-1132

VL - 56

SP - 622

EP - 627

JO - Transfusion

JF - Transfusion

IS - 3

ER -

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

Abstract

Keywords

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