Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations

Christine E. McLaren; Stela McLachlan; Chad P. Garner; Chris D. Vulpe; Victor R. Gordeuk; John H Eckfeldt; Paul C. Adams; Ronald T. Acton; Joseph A. Murray; Catherine Leiendecker-Foster; Beverly M. Snively; Lisa F. Barcellos; James D. Cook; Gordon D. McLaren

doi:10.1371/journal.pone.0038339

Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations

Christine E. McLaren, Stela McLachlan, Chad P. Garner, Chris D. Vulpe, Victor R. Gordeuk, John H Eckfeldt, Paul C. Adams, Ronald T. Acton, Joseph A. Murray, Catherine Leiendecker-Foster, Beverly M. Snively, Lisa F. Barcellos, James D. Cook, Gordon D. McLaren

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

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Abstract

The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤12 μg/L (cases) and controls (SF >100 μg/L in men, SF >50 μg/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7×10^-6) and replicated in African Americans (p = 0.0012).Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p<4.4×10^-5); six SNPs replicated in other ethnicities (p<0.01). SNP rs10904850 in the CUBN gene on 10p13 was associated with serum iron in African Americans (P = 1.0×10^-5). These results confirm known associations with iron measures and give unique evidence of their role in different ethnicities, suggesting origins in a common founder.

Original language	English (US)
Article number	e38339
Journal	PloS one
Volume	7
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0038339
State	Published - Jun 22 2012

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McLaren, C. E., McLachlan, S., Garner, C. P., Vulpe, C. D., Gordeuk, V. R., Eckfeldt, J. H., Adams, P. C., Acton, R. T., Murray, J. A., Leiendecker-Foster, C., Snively, B. M., Barcellos, L. F., Cook, J. D., & McLaren, G. D. (2012). Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations. PloS one, 7(6), Article e38339. https://doi.org/10.1371/journal.pone.0038339

McLaren, CE, McLachlan, S, Garner, CP, Vulpe, CD, Gordeuk, VR, Eckfeldt, JH, Adams, PC, Acton, RT, Murray, JA, Leiendecker-Foster, C, Snively, BM, Barcellos, LF, Cook, JD & McLaren, GD 2012, 'Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations', PloS one, vol. 7, no. 6, e38339. https://doi.org/10.1371/journal.pone.0038339

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abstract = "The existence of multiple inherited disorders of iron metabolism suggests genetic contributions to iron deficiency. We previously performed a genome-wide association study of iron-related single nucleotide polymorphisms (SNPs) using DNA from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤12 μg/L (cases) and controls (SF >100 μg/L in men, SF >50 μg/L in women). We report a follow-up study of white, African-American, Hispanic, and Asian HEIRS participants, analyzed for association between SNPs and eight iron-related outcomes. Three chromosomal regions showed association across multiple populations, including SNPs in the TF and TMPRSS6 genes, and on chromosome 18q21. A novel SNP rs1421312 in TMPRSS6 was associated with serum iron in whites (p = 3.7×10-6) and replicated in African Americans (p = 0.0012).Twenty SNPs in the TF gene region were associated with total iron-binding capacity in whites (p<4.4×10-5); six SNPs replicated in other ethnicities (p<0.01). SNP rs10904850 in the CUBN gene on 10p13 was associated with serum iron in African Americans (P = 1.0×10-5). These results confirm known associations with iron measures and give unique evidence of their role in different ethnicities, suggesting origins in a common founder.",

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Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations

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