Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes

Francesca Clementina Radio, Silvia Majore, Caterina Aurizi, Fiammetta Sorge, Gianfranco Biolcati, Sara Bernabini, Irene Giotti, Francesca Torricelli, Diana Giannarelli, Carmelilia De Bernardo, Paola Grammatico

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Hereditary hemochromatosis (HH) is a heterogeneous disorder of iron metabolism. The most common form of the disease is Classic or type 1 HH, mainly caused by a biallelic missense p.Cys282Tyr (c.845G. > A) mutation in the HFE gene. However, the penetrance of p.Cys282Tyr/p.Cys282Tyr genotype is incomplete in terms of both biochemical and clinical expressivity. Lack of penetrance is thought to be caused by several genetic and environmental factors. Recently, a lot of evidences on HH genetic modifiers were produced, often without conclusive results.We investigated 6 polymorphisms (rs10421768 in HAMP gene, rs235756 in BMP2 gene, rs2230267 in FTL gene, rs1439816 in SLC40A1 gene, rs41295942 in TFR2 gene and rs2111833 in TMPRSS6 gene) with uncertain function in order to further evaluate their role in an independent cohort of 109 HH type 1 patients. Our results make it likely the role of rs10421768, rs235756, rs2230267 and rs1439816 polymorphisms, respectively in HAMP, BMP2, FTL and SLC40A1 genes in HH expressivity. In addition, previous and our findings support a hypothetical multifactorial model of HH, characterized by a principal gene (HFE in HH type 1) and minor genetic and environmental factors that still have to be fully elucidated.

Original languageEnglish
Pages (from-to)71-75
Number of pages5
JournalBlood cells, molecules & diseases
Volume55
Issue number1
DOIs
Publication statusPublished - Jun 1 2015

Fingerprint

Hemochromatosis
Phenotype
Genes
Penetrance
Iron Metabolism Disorders
Genotype
Mutation

Keywords

  • BMP2
  • FTL
  • HAMP
  • Hereditary hemochromatosis
  • Iron overload
  • P.Cys282Tyr
  • Penetrance defect
  • SLC40A1
  • TFR2
  • TMPRSS6

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology
  • Cell Biology

Cite this

Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes. / Radio, Francesca Clementina; Majore, Silvia; Aurizi, Caterina; Sorge, Fiammetta; Biolcati, Gianfranco; Bernabini, Sara; Giotti, Irene; Torricelli, Francesca; Giannarelli, Diana; De Bernardo, Carmelilia; Grammatico, Paola.

In: Blood cells, molecules & diseases, Vol. 55, No. 1, 01.06.2015, p. 71-75.

Research output: Contribution to journalArticle

Radio, Francesca Clementina ; Majore, Silvia ; Aurizi, Caterina ; Sorge, Fiammetta ; Biolcati, Gianfranco ; Bernabini, Sara ; Giotti, Irene ; Torricelli, Francesca ; Giannarelli, Diana ; De Bernardo, Carmelilia ; Grammatico, Paola. / Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes. In: Blood cells, molecules & diseases. 2015 ; Vol. 55, No. 1. pp. 71-75.
@article{3b75aa051dd14cb8a7177efa332f5cd7,
title = "Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes",
abstract = "Hereditary hemochromatosis (HH) is a heterogeneous disorder of iron metabolism. The most common form of the disease is Classic or type 1 HH, mainly caused by a biallelic missense p.Cys282Tyr (c.845G. > A) mutation in the HFE gene. However, the penetrance of p.Cys282Tyr/p.Cys282Tyr genotype is incomplete in terms of both biochemical and clinical expressivity. Lack of penetrance is thought to be caused by several genetic and environmental factors. Recently, a lot of evidences on HH genetic modifiers were produced, often without conclusive results.We investigated 6 polymorphisms (rs10421768 in HAMP gene, rs235756 in BMP2 gene, rs2230267 in FTL gene, rs1439816 in SLC40A1 gene, rs41295942 in TFR2 gene and rs2111833 in TMPRSS6 gene) with uncertain function in order to further evaluate their role in an independent cohort of 109 HH type 1 patients. Our results make it likely the role of rs10421768, rs235756, rs2230267 and rs1439816 polymorphisms, respectively in HAMP, BMP2, FTL and SLC40A1 genes in HH expressivity. In addition, previous and our findings support a hypothetical multifactorial model of HH, characterized by a principal gene (HFE in HH type 1) and minor genetic and environmental factors that still have to be fully elucidated.",
keywords = "BMP2, FTL, HAMP, Hereditary hemochromatosis, Iron overload, P.Cys282Tyr, Penetrance defect, SLC40A1, TFR2, TMPRSS6",
author = "Radio, {Francesca Clementina} and Silvia Majore and Caterina Aurizi and Fiammetta Sorge and Gianfranco Biolcati and Sara Bernabini and Irene Giotti and Francesca Torricelli and Diana Giannarelli and {De Bernardo}, Carmelilia and Paola Grammatico",
year = "2015",
month = "6",
day = "1",
doi = "10.1016/j.bcmd.2015.04.001",
language = "English",
volume = "55",
pages = "71--75",
journal = "Blood Cells, Molecules, and Diseases",
issn = "1079-9796",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes

AU - Radio, Francesca Clementina

AU - Majore, Silvia

AU - Aurizi, Caterina

AU - Sorge, Fiammetta

AU - Biolcati, Gianfranco

AU - Bernabini, Sara

AU - Giotti, Irene

AU - Torricelli, Francesca

AU - Giannarelli, Diana

AU - De Bernardo, Carmelilia

AU - Grammatico, Paola

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Hereditary hemochromatosis (HH) is a heterogeneous disorder of iron metabolism. The most common form of the disease is Classic or type 1 HH, mainly caused by a biallelic missense p.Cys282Tyr (c.845G. > A) mutation in the HFE gene. However, the penetrance of p.Cys282Tyr/p.Cys282Tyr genotype is incomplete in terms of both biochemical and clinical expressivity. Lack of penetrance is thought to be caused by several genetic and environmental factors. Recently, a lot of evidences on HH genetic modifiers were produced, often without conclusive results.We investigated 6 polymorphisms (rs10421768 in HAMP gene, rs235756 in BMP2 gene, rs2230267 in FTL gene, rs1439816 in SLC40A1 gene, rs41295942 in TFR2 gene and rs2111833 in TMPRSS6 gene) with uncertain function in order to further evaluate their role in an independent cohort of 109 HH type 1 patients. Our results make it likely the role of rs10421768, rs235756, rs2230267 and rs1439816 polymorphisms, respectively in HAMP, BMP2, FTL and SLC40A1 genes in HH expressivity. In addition, previous and our findings support a hypothetical multifactorial model of HH, characterized by a principal gene (HFE in HH type 1) and minor genetic and environmental factors that still have to be fully elucidated.

AB - Hereditary hemochromatosis (HH) is a heterogeneous disorder of iron metabolism. The most common form of the disease is Classic or type 1 HH, mainly caused by a biallelic missense p.Cys282Tyr (c.845G. > A) mutation in the HFE gene. However, the penetrance of p.Cys282Tyr/p.Cys282Tyr genotype is incomplete in terms of both biochemical and clinical expressivity. Lack of penetrance is thought to be caused by several genetic and environmental factors. Recently, a lot of evidences on HH genetic modifiers were produced, often without conclusive results.We investigated 6 polymorphisms (rs10421768 in HAMP gene, rs235756 in BMP2 gene, rs2230267 in FTL gene, rs1439816 in SLC40A1 gene, rs41295942 in TFR2 gene and rs2111833 in TMPRSS6 gene) with uncertain function in order to further evaluate their role in an independent cohort of 109 HH type 1 patients. Our results make it likely the role of rs10421768, rs235756, rs2230267 and rs1439816 polymorphisms, respectively in HAMP, BMP2, FTL and SLC40A1 genes in HH expressivity. In addition, previous and our findings support a hypothetical multifactorial model of HH, characterized by a principal gene (HFE in HH type 1) and minor genetic and environmental factors that still have to be fully elucidated.

KW - BMP2

KW - FTL

KW - HAMP

KW - Hereditary hemochromatosis

KW - Iron overload

KW - P.Cys282Tyr

KW - Penetrance defect

KW - SLC40A1

KW - TFR2

KW - TMPRSS6

UR - http://www.scopus.com/inward/record.url?scp=84929161673&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929161673&partnerID=8YFLogxK

U2 - 10.1016/j.bcmd.2015.04.001

DO - 10.1016/j.bcmd.2015.04.001

M3 - Article

C2 - 25976471

AN - SCOPUS:84929161673

VL - 55

SP - 71

EP - 75

JO - Blood Cells, Molecules, and Diseases

JF - Blood Cells, Molecules, and Diseases

SN - 1079-9796

IS - 1

ER -