Abstract
BackgroundAim of this study was to evaluate whether the A736V TMPRSS6 polymorphism, a major genetic determinant of iron metabolism in healthy subjects, influences serum levels of hepcidin, the hormone regulating iron metabolism, and erythropoiesis in chronic hemodialysis (CHD).MethodsTo this end, we considered 199 CHD patients from Northern Italy (157 with hepcidin evaluation), and 188 healthy controls without iron deficiency, matched for age and gender. Genetic polymorphisms were evaluated by allele specific polymerase chain reaction assays, and hepcidin quantified by mass spectrometry.ResultsSerum hepcidin levels were not different between the whole CHD population and controls (median 7.1, interquartile range (IQR) 0.55-17.1 vs. 7.4, 4.5-17.9 nM, respectively), but were higher in the CHD subgroup after exclusion of subjects with relative iron deficiency (p = 0.04). In CHD patients, the A736V TMPRSS6 polymorphism influenced serum hepcidin levels in individuals positive for mutations in the HFE gene of hereditary hemochromatosis (p < 0.0001). In particular, the TMPRSS6 736 V variant was associated with higher hepcidin levels (p = 0.017). At multivariate analysis, HFE and A736V TMPRSS6 genotypes predicted serum hepcidin independently of ferritin and C reactive protein (p = 0.048). In patients without acute inflammation and overt iron deficiency (C reactive protein <1 mg/dl and ferritin >30 ng/ml; n = 86), hepcidin was associated with lower mean corpuscular volume (p = 0.002), suggesting that it contributed to iron-restricted erythropoiesis. In line with previous results, in patients without acute inflammation and severe iron deficiency the “high hepcidin” 736 V TMPRSS6 variant was associated with higher erythropoietin maintenance dose (p = 0.016), independently of subclinical inflammation (p = 0.02).ConclusionsThe A736V TMPRSS6 genotype influences hepcidin levels, erythropoiesis, and anemia management in CHD patients. Evaluation of the effect of TMPRSS6 genotype on clinical outcomes in prospective studies in CHD may be useful to predict the outcomes of hepcidin manipulation, and to guide treatment personalization by optimizing anemia management.
Highlights
Aim of this study was to evaluate whether the A736V Trans-membrane protease serine 6 (TMPRSS6) polymorphism, a major genetic determinant of iron metabolism in healthy subjects, influences serum levels of hepcidin, the hormone regulating iron metabolism, and erythropoiesis in chronic hemodialysis (CHD)
In the hypothesis that increased hepcidin is involved in the deregulation of iron metabolism and the anemia of CHD, the aim of this study were to evaluate whether the TMPRSS6 A736V polymorphism influences hepcidin levels and erythropoiesis parameters in CHD patients
In patients without severe iron deficiency and with normal C reactive protein (CRP) levels (Table 4), hepcidin25 was correlated with ferritin, and inversely correlated with TF and mean corpuscular volume (MCV) values
Summary
Aim of this study was to evaluate whether the A736V TMPRSS6 polymorphism, a major genetic determinant of iron metabolism in healthy subjects, influences serum levels of hepcidin, the hormone regulating iron metabolism, and erythropoiesis in chronic hemodialysis (CHD). Patients with end stage renal disease (ESRD) undergoing chronic hemodialysis (CHD) are commonly affected by anemia, which is related to erythropoietin (Epo) deficiency, blood losses, and chronic inflammation [1]. Upregulation of serum levels of hepcidin, the hepatic hormone regulating systemic iron metabolism, has been proposed to explain the alterations of iron metabolism of CHD patients and the resistance to anemia treatment [5,6]. Increased hepcidin in ESRD may result from reduced glomerular filtration, subclinical inflammation, as hepcidin is an acute phase reactant, and increased iron stores due to chronic supplementation. Hepcidin is downregulated by anemia, hypoxia, and erythropoietin [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
