GNPAT rs11558492 is not a major modifier of iron status

Study of Italian hemochromatosis patients and blood donors

Federico Greni, Luca Valenti, Raffaella Mariani, Irene Pelloni, Raffaela Rametta, Fabiana Busti, Giulia Ravasi, Domenico Girelli, Silvia Fargion, Stefania Galimberti, Alberto Piperno, Sara Pelucchi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background and Aim. HFE-related Hemochromatosis (HH) is characterized by marked phenotype heterogeneity, probably due to the combined action of acquired and genetic factors. Among them, GNPAT rs11558492 was proposed as genetic modifier of iron status, but results are still controversial. To shed light on these discrepancies, we genotyped 298 Italian p.C282Y homozygotes and 169 healthy controls. Material and methods. Allele and genotype frequencies were analysed and compared with those reported in Exome Variant Server (EVS). To explore the role of rs11558492 as a potential modifier of iron status, serum ferritin (SF), liver iron concentration (LIC) and iron removed (IR) were studied according to allele and genotype frequencies. In addition, the effect of the SNP on liver fibrosis was examined comparing patients with absent/mild-moderate fibrosis to those with severe fibrosis-cirrhosis. Results. GNPAT rs11558492 minor allele (G) frequency (MAF) was 20.3% in HFE-HH, 17.2% in controls and 20.6% in EVS database. Genotype frequencies were 64% and 69.2% (AA), 31.2% and 27.2% (AG), 4.8% and 3.6% (GG) in HFE-HH and controls, respectively. No significant differences were found comparing genotype and allele frequencies even selecting subgroups of only-males with extreme phenotypes and low alcohol intake. SF, IR and LIC levels did not significantly differ according to rs11558492 genotypes. Also, MAF did not differ between patients with absent/mild fibrosis and severe fibrosis/cirrhosis. Conclusions. Our findings indicate that GNPAT rs11558492 is not a major modifier of iron status and is not associated with liver fibrosis in HFE-HH patients.

Original languageEnglish
Pages (from-to)451-456
Number of pages6
JournalAnnals of Hepatology
Volume16
Issue number3
DOIs
Publication statusPublished - 2017

Fingerprint

Hemochromatosis
Blood Donors
Iron
Fibrosis
Gene Frequency
Genotype
Exome
Ferritins
Liver Cirrhosis
Phenotype
Liver
Homozygote
Serum
Single Nucleotide Polymorphism
Alcohols
Databases

Keywords

  • Glyceronephosphate o-acyltransferase
  • Hereditary hemochromatosis
  • Iron overload
  • Polymorphism
  • Serum ferritin

ASJC Scopus subject areas

  • Hepatology

Cite this

GNPAT rs11558492 is not a major modifier of iron status : Study of Italian hemochromatosis patients and blood donors. / Greni, Federico; Valenti, Luca; Mariani, Raffaella; Pelloni, Irene; Rametta, Raffaela; Busti, Fabiana; Ravasi, Giulia; Girelli, Domenico; Fargion, Silvia; Galimberti, Stefania; Piperno, Alberto; Pelucchi, Sara.

In: Annals of Hepatology, Vol. 16, No. 3, 2017, p. 451-456.

Research output: Contribution to journalArticle

Greni, F, Valenti, L, Mariani, R, Pelloni, I, Rametta, R, Busti, F, Ravasi, G, Girelli, D, Fargion, S, Galimberti, S, Piperno, A & Pelucchi, S 2017, 'GNPAT rs11558492 is not a major modifier of iron status: Study of Italian hemochromatosis patients and blood donors', Annals of Hepatology, vol. 16, no. 3, pp. 451-456. https://doi.org/10.5604/16652681.1235489
Greni, Federico ; Valenti, Luca ; Mariani, Raffaella ; Pelloni, Irene ; Rametta, Raffaela ; Busti, Fabiana ; Ravasi, Giulia ; Girelli, Domenico ; Fargion, Silvia ; Galimberti, Stefania ; Piperno, Alberto ; Pelucchi, Sara. / GNPAT rs11558492 is not a major modifier of iron status : Study of Italian hemochromatosis patients and blood donors. In: Annals of Hepatology. 2017 ; Vol. 16, No. 3. pp. 451-456.
@article{5dad4fadf75f434c9bd18d11c1d8b699,
title = "GNPAT rs11558492 is not a major modifier of iron status: Study of Italian hemochromatosis patients and blood donors",
abstract = "Background and Aim. HFE-related Hemochromatosis (HH) is characterized by marked phenotype heterogeneity, probably due to the combined action of acquired and genetic factors. Among them, GNPAT rs11558492 was proposed as genetic modifier of iron status, but results are still controversial. To shed light on these discrepancies, we genotyped 298 Italian p.C282Y homozygotes and 169 healthy controls. Material and methods. Allele and genotype frequencies were analysed and compared with those reported in Exome Variant Server (EVS). To explore the role of rs11558492 as a potential modifier of iron status, serum ferritin (SF), liver iron concentration (LIC) and iron removed (IR) were studied according to allele and genotype frequencies. In addition, the effect of the SNP on liver fibrosis was examined comparing patients with absent/mild-moderate fibrosis to those with severe fibrosis-cirrhosis. Results. GNPAT rs11558492 minor allele (G) frequency (MAF) was 20.3{\%} in HFE-HH, 17.2{\%} in controls and 20.6{\%} in EVS database. Genotype frequencies were 64{\%} and 69.2{\%} (AA), 31.2{\%} and 27.2{\%} (AG), 4.8{\%} and 3.6{\%} (GG) in HFE-HH and controls, respectively. No significant differences were found comparing genotype and allele frequencies even selecting subgroups of only-males with extreme phenotypes and low alcohol intake. SF, IR and LIC levels did not significantly differ according to rs11558492 genotypes. Also, MAF did not differ between patients with absent/mild fibrosis and severe fibrosis/cirrhosis. Conclusions. Our findings indicate that GNPAT rs11558492 is not a major modifier of iron status and is not associated with liver fibrosis in HFE-HH patients.",
keywords = "Glyceronephosphate o-acyltransferase, Hereditary hemochromatosis, Iron overload, Polymorphism, Serum ferritin",
author = "Federico Greni and Luca Valenti and Raffaella Mariani and Irene Pelloni and Raffaela Rametta and Fabiana Busti and Giulia Ravasi and Domenico Girelli and Silvia Fargion and Stefania Galimberti and Alberto Piperno and Sara Pelucchi",
year = "2017",
doi = "10.5604/16652681.1235489",
language = "English",
volume = "16",
pages = "451--456",
journal = "Annals of Hepatology",
issn = "1665-2681",
publisher = "Mexican Association of Hepatology",
number = "3",

}

TY - JOUR

T1 - GNPAT rs11558492 is not a major modifier of iron status

T2 - Study of Italian hemochromatosis patients and blood donors

AU - Greni, Federico

AU - Valenti, Luca

AU - Mariani, Raffaella

AU - Pelloni, Irene

AU - Rametta, Raffaela

AU - Busti, Fabiana

AU - Ravasi, Giulia

AU - Girelli, Domenico

AU - Fargion, Silvia

AU - Galimberti, Stefania

AU - Piperno, Alberto

AU - Pelucchi, Sara

PY - 2017

Y1 - 2017

N2 - Background and Aim. HFE-related Hemochromatosis (HH) is characterized by marked phenotype heterogeneity, probably due to the combined action of acquired and genetic factors. Among them, GNPAT rs11558492 was proposed as genetic modifier of iron status, but results are still controversial. To shed light on these discrepancies, we genotyped 298 Italian p.C282Y homozygotes and 169 healthy controls. Material and methods. Allele and genotype frequencies were analysed and compared with those reported in Exome Variant Server (EVS). To explore the role of rs11558492 as a potential modifier of iron status, serum ferritin (SF), liver iron concentration (LIC) and iron removed (IR) were studied according to allele and genotype frequencies. In addition, the effect of the SNP on liver fibrosis was examined comparing patients with absent/mild-moderate fibrosis to those with severe fibrosis-cirrhosis. Results. GNPAT rs11558492 minor allele (G) frequency (MAF) was 20.3% in HFE-HH, 17.2% in controls and 20.6% in EVS database. Genotype frequencies were 64% and 69.2% (AA), 31.2% and 27.2% (AG), 4.8% and 3.6% (GG) in HFE-HH and controls, respectively. No significant differences were found comparing genotype and allele frequencies even selecting subgroups of only-males with extreme phenotypes and low alcohol intake. SF, IR and LIC levels did not significantly differ according to rs11558492 genotypes. Also, MAF did not differ between patients with absent/mild fibrosis and severe fibrosis/cirrhosis. Conclusions. Our findings indicate that GNPAT rs11558492 is not a major modifier of iron status and is not associated with liver fibrosis in HFE-HH patients.

AB - Background and Aim. HFE-related Hemochromatosis (HH) is characterized by marked phenotype heterogeneity, probably due to the combined action of acquired and genetic factors. Among them, GNPAT rs11558492 was proposed as genetic modifier of iron status, but results are still controversial. To shed light on these discrepancies, we genotyped 298 Italian p.C282Y homozygotes and 169 healthy controls. Material and methods. Allele and genotype frequencies were analysed and compared with those reported in Exome Variant Server (EVS). To explore the role of rs11558492 as a potential modifier of iron status, serum ferritin (SF), liver iron concentration (LIC) and iron removed (IR) were studied according to allele and genotype frequencies. In addition, the effect of the SNP on liver fibrosis was examined comparing patients with absent/mild-moderate fibrosis to those with severe fibrosis-cirrhosis. Results. GNPAT rs11558492 minor allele (G) frequency (MAF) was 20.3% in HFE-HH, 17.2% in controls and 20.6% in EVS database. Genotype frequencies were 64% and 69.2% (AA), 31.2% and 27.2% (AG), 4.8% and 3.6% (GG) in HFE-HH and controls, respectively. No significant differences were found comparing genotype and allele frequencies even selecting subgroups of only-males with extreme phenotypes and low alcohol intake. SF, IR and LIC levels did not significantly differ according to rs11558492 genotypes. Also, MAF did not differ between patients with absent/mild fibrosis and severe fibrosis/cirrhosis. Conclusions. Our findings indicate that GNPAT rs11558492 is not a major modifier of iron status and is not associated with liver fibrosis in HFE-HH patients.

KW - Glyceronephosphate o-acyltransferase

KW - Hereditary hemochromatosis

KW - Iron overload

KW - Polymorphism

KW - Serum ferritin

UR - http://www.scopus.com/inward/record.url?scp=85018374268&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018374268&partnerID=8YFLogxK

U2 - 10.5604/16652681.1235489

DO - 10.5604/16652681.1235489

M3 - Article

VL - 16

SP - 451

EP - 456

JO - Annals of Hepatology

JF - Annals of Hepatology

SN - 1665-2681

IS - 3

ER -