Radio Francesca Clementina, Majore Silvia, Aurizi Caterina, Sorge Fiammetta, Biolcati Gianfranco, Bernabini Sara, Giotti Irene, Torricelli Francesca, Giannarelli Diana, De Bernardo Carmelilia, Grammatico Paola
Medical Genetics, Molecular Medicine Department, Sapienza University of Rome, San Camillo-Forlanini Hospital, Rome, Italy.
Medical Genetics, Molecular Medicine Department, Sapienza University of Rome, San Camillo-Forlanini Hospital, Rome, Italy.
Blood Cells Mol Dis. 2015 Jun;55(1):71-5. doi: 10.1016/j.bcmd.2015.04.001. Epub 2015 Apr 16.
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.
遗传性血色素沉着症（HH）是一种铁代谢的异质性疾病。该疾病最常见的形式是经典型或1型HH，主要由HFE基因中的双等位基因错义p.Cys282Tyr（c.845G>A）突变引起。然而，就生化和临床表现而言，p.Cys282Tyr/p.Cys282Tyr基因型的外显率并不完全。外显率缺乏被认为是由多种遗传和环境因素导致的。最近，产生了许多关于HH基因修饰因子的证据，但往往没有确凿的结果。我们研究了6个功能不确定的多态性位点（HAMP基因中的rs10421768、BMP2基因中的rs235756、FTL基因中的rs2230267、SLC40A1基因中的rs1439816、TFR2基因中的rs41295942和TMPRSS6基因中的rs2111833），以便在109例1型HH患者的独立队列中进一步评估它们的作用。我们的结果表明，rs10421768、rs235756、rs2230267和rs1439816多态性位点分别在HAMP、BMP2、FTL和SLC40A1基因的HH表达中发挥作用。此外，先前的研究结果和我们的发现支持了一个关于HH的假设性多因素模型，其特征是一个主基因（1型HH中的HFE）以及仍有待充分阐明的次要遗传和环境因素。
