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Associations between Single Nucleotide Polymorphisms in Iron-Related Genes and Iron Status in Multiethnic Populations
- Author(s): McLaren, Christine E.
- McLachlan, Stela
- Garner, Chad P.
- Vulpe, Chris D.
- Gordeuk, Victor R.
- Eckfeldt, John H.
- Adams, Paul C.
- Acton, Ronald T.
- Murray, Joseph A.
- Leiendecker-Foster, Catherine
- Snively, Beverly M.
- Barcellos, Lisa F.
- Cook, James D.
- McLaren, Gordon D.
- et al.
Published Web Location
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3382217/pdf/pone.0038339.pdfAbstract
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.