Down-regulation of hepcidin in porphyria cutanea tarda

被引：30

作者：

Ajioka, Richard S. ^{[1
]}

Phillips, John D. ^{[1
]}

Weiss, Robert B. ^{[2
]}

Dunn, Diane M. ^{[2
]}

Smit, Maria W. ^{[3
]}

Proll, Sean C. ^{[3
]}

Katze, Michael G. ^{[3
]}

Kushner, James P. ^{[1
]}

机构：

[1] Univ Utah, Sch Med, Div Hematol, Salt Lake City, UT 84132 USA

[2] Univ Utah, Sch Med, Dept Human Genet, Salt Lake City, UT 84132 USA

[3] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA

来源：

BLOOD | 2008年 / 112卷 / 12期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1182/blood-2008-02-138222

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Hepatic siderosis is common in patients with porphyria cutanea tarda (PCT). Mutations in the hereditary hemochromatosis (hh) gene (HFE) explain the siderosis in approximately 20% patients, suggesting that the remaining occurrences result from additional genetic and environmental factors. Two genes known to modify iron loading in hh are hepcidin (HAMP) and hemojuvelin (HJV). To determine if mutations in or expression of these genes influenced iron overload in PCT, we compared sequences of HAMP and HJV in 96 patients with PCT and 88 HFE C282Y homozygotes with marked hepatic iron overload. We also compared hepatic expression of these and other iron-related genes in a group of patients with PCT and hh. Two intronic polymorphisms in HJV were associated with elevated serum ferritin in HFE C282Y homozygotes. No exonic polymorphisms were identified. Sequencing of HAMP revealed exonic polymorphisms in 2 patients with PCT: heterozygosity for a G -> Atransition (G71D substitution) in one and heterozygosity for an A -> G transition (K83R substitution) in the other. Hepatic HAMP expression in patients with PCT was significantly reduced, regardless of HFE genotype, when compared with patients with hh but without PCT with comparable iron overload. These data indicate that the hepatic siderosis associated with PCT likely results from dysregulated HAMP. (Blood. 2008; 112: 4723-4728)

引用

页码：4723 / 4728

页数：6