A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis

Constantine, CC; Anderson, GJ; Vulpe, CD; McLaren, CE; Bahlo, M; Yeap, HL; Gertig, DM; Osborne, NJ; Bertalli, NA; Beckman, KB; Chen, V; Matak, P; McKie, AT; Delatycki, MB; Olynyk, JK; English, DR; Southey, MC; Giles, GG; Hopper, JL; Allen, KJ; Gurrin, LC

Author(s): Constantine, CC; Anderson, GJ; Vulpe, CD; McLaren, CE; Bahlo, M; Yeap, HL; Gertig, DM; Osborne, NJ; Bertalli, NA; Beckman, KB; Chen, V; Matak, P; McKie, AT; Delatycki, MB; Olynyk, JK; English, DR; Southey, MC; Giles, GG; Hopper, JL; Allen, KJ; Gurrin, LC;
Details: Publication Year 2009-10,Volume 147,Issue #1,Page 140-149
Journal Title: BRITISH JOURNAL OF HAEMATOLOGY
Publication Type: Journal Article
Abstract: P>There is emerging evidence that there are genetic modifiers of iron indices for HFE gene mutation carriers at risk of hereditary hemochromatosis. A random sample, stratified by HFE genotype, of 863 from a cohort of 31 192 people of northern European descent provided blood samples for genotyping of 476 single nucleotide polymorphisms (SNPs) in 44 genes involved in iron metabolism. Single SNP association testing, using linear regression models adjusted for sex, menopause and HFE genotype, was conducted for four continuously distributed outcomes: serum ferritin (log transformed), transferrin saturation, serum transferrin, and serum iron. The SNP rs884409 in CYBRD1 is a novel modifier specific to HFE C282Y homozygotes. Median unadjusted serum ferritin concentration decreased from 1194 mu g/l (N = 27) to 387 mu g/l (N = 16) for male C282Y homozygotes and from 357 mu g/l (N = 42) to 69 mu g/l (N = 12) for females, comparing those with no copies to those with one copy of rs884409. Functional testing of this CYBRD1 promoter polymorphism using a heterologous expression assay resulted in a 30% decrease in basal promoter activity relative to the common genotype (P = 0 center dot 004). This putative genetic modifier of iron overload expression accounts for 11% (95% CI 0 center dot 4%, 22 center dot 6%) of the variance in serum ferritin levels of C282Y homozygotes.
Publisher: WILEY-BLACKWELL PUBLISHING, INC
Keywords: TRANSFERRIN SATURATION; IRON-OVERLOAD; NATURAL-HISTORY; TMPRSS6 GENE; POPULATION; MUTATIONS; DISEASE; C282Y; BMP6; POLYMORPHISMS
Publisher's Version: https://doi.org/10.1111/j.1365-2141.2009.07843.x
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2009-10-01 12:00:00