Rabbit Anti-Human HAMP Polyclonal Antibody

Juvenile hemochromatosis is a rare autosomal recessive disease due to variants in the Hemojuvelin (HJV) gene. Although biological features mimic HFE hemochromatosis, clinical presentation is worst with massive iron overload diagnosed during childhood. Our study describes clinical features and results of genetic testing for a group of patients initially referred for a hepcidino-deficiency syndrome and for whom HJV hemochromatosis was finally diagnosed. 662 patients with iron overload and high serum transferrin saturation were tested, and five genes (HFE, HJV, HAMP, TFR2, SLC40A1) were sequenced. Among our cohort, ten unrelated patients were diagnosed with HJV hemochromatosis. Genetic testing revealed five previously published and five undescribed variants: p.Arg41Pro, p.His180Arg, p.Lys299G1u, p.Cys361Arg and p.A1a384Val. Surprisingly, this study revealed a late age of onset in some patients, contrasting with the commonly accepted definition of "juvenile" hemochromatosis. Five of our patients were 30 years old or older, including two very late discoveries. Biological features and severity of iron overload were similar in younger and older patients. Our study brings new insight on HJV hemochromatosis showing that mild phenotype and late onset are possible. Genetic testing for HJV variants should thus be performed for all patients displaying a non-p.Cys282Tyr homozygous HFE hemochromatosis with hepcidin deficiency phenotype.

Background: Iron deficiency is extremely common after bariatric surgery. HEPCIDIN, encoded by Hamp, is a hormone that negatively regulates iron homeostasis. Objectives: We aimed to investigate the alteration of Hamp expression and related regulatory factors to explore the probable role of DNA methylation in modulating Hamp expression in the context of iron deficiency after bariatric surgery. Setting: Laboratories of Diabetes Institute. Methods: RNA-seq was performed using rat liver tissue after either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy surgery to identify differentially expressed genes between the bariatric surgery and sham group. Hamp expression were measured by quantitative polymerase chain reaction and enzymelinked immunosorbent assay, respectively. The DNA methylation level was determined using MassAR-RAY EpiTYPER. Iron status, erythrocyte parameters, and inflammation factors were assessed. Results: RNA-seq data showed that liver Hamp expression changed most dramatically in RYGB-operated rats. Both the mRNA expression of Hamp and the abundance of its protein product HEPCIDIN-25 decreased markedly after bariatric surgery compared with sham, while sleeve gastrectomy-operated rats showed marginally higher Hamp expression than RYGB-operated rats. The DNA methylation level of the Hamp promoter region was significant higher in RYGB-operated rats than sham, while sleeve gastrectomy rats increased slightly in DNA methylation. Consistent with the change of HEPCIDIN-25, serum iron was significantly lower for both bariatric groups than sham and particularly low in RYGB. Conclusions: Our data demonstrate that elevated DNA methylation of the Hamp promoter region suppresses its expression, this epigenetic modification likely occurs in reaction to iron deficiency after bariatric surgery, helping to maintain system iron homeostasis. (C) 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.