Background: Aim of this study was to evaluate whether the A736V TMPRSS6 polymorphism, a major geneticdeterminant of iron metabolism in healthy subjects, influences serum levels of hepcidin, the hormone regulatingiron metabolism, and erythropoiesis in chronic hemodialysis (CHD).Methods: To this end, we considered 199 CHD patients from Northern Italy (157 with hepcidin evaluation), and 188healthy controls without iron deficiency, matched for age and gender. Genetic polymorphisms were evaluated byallele specific polymerase chain reaction assays, and hepcidin quantified by mass spectrometry.Results: Serum 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 afterexclusion of subjects with relative iron deficiency (p = 0.04). In CHD patients, the A736V TMPRSS6 polymorphisminfluenced serum hepcidin levels in individuals positive for mutations in the HFE gene of hereditaryhemochromatosis (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 offerritin and C reactive protein (p = 0.048). In patients without acute inflammation and overt iron deficiency (Creactive protein <1 mg/dl and ferritin >30 ng/ml; n = 86), hepcidin was associated with lower mean corpuscularvolume (p = 0.002), suggesting that it contributed to iron-restricted erythropoiesis. In line with previous results, inpatients without acute inflammation and severe iron deficiency the “high hepcidin” 736 V TMPRSS6 variant wasassociated with higher erythropoietin maintenance dose (p = 0.016), independently of subclinical inflammation(p = 0.02).Conclusions: The A736V TMPRSS6 genotype influences hepcidin levels, erythropoiesis, and anemia management inCHD patients. Evaluation of the effect of TMPRSS6 genotype on clinical outcomes in prospective studies in CHDmay be useful to predict the outcomes of hepcidin manipulation, and to guide treatment personalization byoptimizing anemia management.

The A736V TMPRSS6 polymorphism influences hepcidin and iron metabolism in chronic hemodialysis patients: TMPRSS6 and hepcidin in hemodialysis.

GIRELLI, Domenico;CAMPOSTRINI, Natascia;
2013

Abstract

Background: Aim of this study was to evaluate whether the A736V TMPRSS6 polymorphism, a major geneticdeterminant of iron metabolism in healthy subjects, influences serum levels of hepcidin, the hormone regulatingiron metabolism, and erythropoiesis in chronic hemodialysis (CHD).Methods: To this end, we considered 199 CHD patients from Northern Italy (157 with hepcidin evaluation), and 188healthy controls without iron deficiency, matched for age and gender. Genetic polymorphisms were evaluated byallele specific polymerase chain reaction assays, and hepcidin quantified by mass spectrometry.Results: Serum 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 afterexclusion of subjects with relative iron deficiency (p = 0.04). In CHD patients, the A736V TMPRSS6 polymorphisminfluenced serum hepcidin levels in individuals positive for mutations in the HFE gene of hereditaryhemochromatosis (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 offerritin and C reactive protein (p = 0.048). In patients without acute inflammation and overt iron deficiency (Creactive protein <1 mg/dl and ferritin >30 ng/ml; n = 86), hepcidin was associated with lower mean corpuscularvolume (p = 0.002), suggesting that it contributed to iron-restricted erythropoiesis. In line with previous results, inpatients without acute inflammation and severe iron deficiency the “high hepcidin” 736 V TMPRSS6 variant wasassociated with higher erythropoietin maintenance dose (p = 0.016), independently of subclinical inflammation(p = 0.02).Conclusions: The A736V TMPRSS6 genotype influences hepcidin levels, erythropoiesis, and anemia management inCHD patients. Evaluation of the effect of TMPRSS6 genotype on clinical outcomes in prospective studies in CHDmay be useful to predict the outcomes of hepcidin manipulation, and to guide treatment personalization byoptimizing anemia management.
Anemia; Chronic kidney disease; Erythropoietin; Genetics; Inflammation; Iron; Hemodialysis; Hepcidin; Hfe gene; Matriptase-2; Tmprss6
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/633351
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