Journal
PLOS ONE
Volume 7, Issue 6, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0038339
Keywords
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Categories
Funding
- National Heart, Lung, and Blood Institute [R01 HL083328]
- United States National Institutes of Health [R01DK57892]
- Department of Veterans Affairs
- NHLBI
- University of Minnesota [N01-HC-05185]
- Howard University [N01-HC-05186]
- University of Alabama at Birmingham [N01-HC-05188]
- Kaiser Permanente Center for Health Research [N01-HC-05189]
- University of California, Irvine [N01-HC-05190]
- London Health Sciences Centre [N01-HC-05191]
- Wake Forest University [N01-HC-05192]
- University of Alabama at Birmingham General Clinical Research Center [M01-RR00032]
- Southern Iron Disorders Center
- Howard University GCRC [M01-RR10284]
- Howard University Research Scientist Award from National Heart, Lung, and Blood Institute [UH1-HL03679-05]
- Office of Research on Minority Health
- grant UC Irvine from General Clinical Research Centers Program of the National Center for Research Resources National Institutes of Health [M01RR 00827-29]
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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 mu g/L (cases) and controls (SF > 100 mu g/L in men, SF>50 mu g/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 = 3.7x10(-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 < 4.4x10(-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 = 1.0x10(-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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