title: Associations between single nucleotide polymorphisms in iron-related genes and iron status in multiethnic populations.
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.
authors: Department of Epidemiology, University of California Irvine, Irvine, California, United States of America. cmclaren@uci.edu
authors: Christine E
authors: CE
authors: McLaren
authors: Stela
authors: S
authors: McLachlan
authors: Chad P
authors: CP
authors: Garner
authors: Chris D
authors: CD
authors: Vulpe
authors: Victor R
authors: VR
authors: Gordeuk
authors: John H
authors: JH
authors: Eckfeldt
authors: Paul C
authors: PC
authors: Adams
authors: Ronald T
authors: RT
authors: Acton
authors: Joseph A
authors: JA
authors: Murray
authors: Catherine
authors: C
authors: Leiendecker-Foster
authors: Beverly M
authors: BM
authors: Snively
authors: Lisa F
authors: LF
authors: Barcellos
authors: James D
authors: JD
authors: Cook
authors: Gordon D
authors: GD
authors: McLaren
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D015415:Biomarkers / Q000032:analysis; D002140:California / Q000453:epidemiology; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics / Q000706:statistics & numerical data; D006801:Humans; D007501:Iron / Q000097:blood*; D019190:Iron Overload / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human