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PLoS By Category | Recent PLoS Articles
Hematology

Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations
Published: Friday, June 22, 2012
Author: Christine E. McLaren et al.

by 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

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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