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

Pelusi S, Girelli D, Rametta R, Campostrini N, Alfieri C, Traglia M, Dongiovanni P, Como G, Toniolo D, Camaschella C, Messa P, Fargion S, Valenti L - BMC Nephrol (2013)

Bottom Line: 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathophysiology and Transplantation, Internal Medicine, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy.

ABSTRACT

Background: 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).

Methods: To 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.

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 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).

Conclusions: The 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.

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Effect of HFE C282Y and H63D genotype status (wild-type, heterozygosity for the H63D mutation, other genotypes) on hepcidin-25 levels (panel A), and hepcidin-25 / ferritin ratio (panel B) in 155 CHD patients from Northern Italy.
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Figure 1: Effect of HFE C282Y and H63D genotype status (wild-type, heterozygosity for the H63D mutation, other genotypes) on hepcidin-25 levels (panel A), and hepcidin-25 / ferritin ratio (panel B) in 155 CHD patients from Northern Italy.

Mentions: The effect of HFE genotype (wild-type, heterozygosity for C282Y and H63D mutations, and other genotypes) on hepcidin-25 in CHD patients is shown in Figure 1A. Hepcidin-25 was lower in patients with HFE mutations than in those without (p = 0.01), in particular in those carrying the C282Y mutation or homozygous for the H63D mutation (p = 0.0004). The effect of HFE genotype on the H/F ratio is shown in Figure 1B. The H/F ratio was lower in patients with HFE mutations than in those without (p = 0.04). Therefore, we grouped together patients with any HFE mutation in further analyses, in order to better characterize the effect of TMPRSS6 genotype.


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

Pelusi S, Girelli D, Rametta R, Campostrini N, Alfieri C, Traglia M, Dongiovanni P, Como G, Toniolo D, Camaschella C, Messa P, Fargion S, Valenti L - BMC Nephrol (2013)

Effect of HFE C282Y and H63D genotype status (wild-type, heterozygosity for the H63D mutation, other genotypes) on hepcidin-25 levels (panel A), and hepcidin-25 / ferritin ratio (panel B) in 155 CHD patients from Northern Italy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585892&req=5

Figure 1: Effect of HFE C282Y and H63D genotype status (wild-type, heterozygosity for the H63D mutation, other genotypes) on hepcidin-25 levels (panel A), and hepcidin-25 / ferritin ratio (panel B) in 155 CHD patients from Northern Italy.
Mentions: The effect of HFE genotype (wild-type, heterozygosity for C282Y and H63D mutations, and other genotypes) on hepcidin-25 in CHD patients is shown in Figure 1A. Hepcidin-25 was lower in patients with HFE mutations than in those without (p = 0.01), in particular in those carrying the C282Y mutation or homozygous for the H63D mutation (p = 0.0004). The effect of HFE genotype on the H/F ratio is shown in Figure 1B. The H/F ratio was lower in patients with HFE mutations than in those without (p = 0.04). Therefore, we grouped together patients with any HFE mutation in further analyses, in order to better characterize the effect of TMPRSS6 genotype.

Bottom Line: 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathophysiology and Transplantation, Internal Medicine, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy.

ABSTRACT

Background: 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).

Methods: To 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.

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 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).

Conclusions: The 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.

Show MeSH
Related in: MedlinePlus