Poster – 02
THE ROLE OF TMPRSS6 GENE VARIANTS IN DIFFERENT TYPES OF IRON DEFICIENCY ANAEMIA – FROM THE RARE SEVERE HEREDITARY IRIDA TO THE COMMON MILD ACQUIRED IDA
Paula Faustino 1, Lúcia Gonçalves 1, Gustavo Jesus 2, Celina Afonso 3, Albertina Vieira 4, Rita Maia 5, Armandina Miranda 6, Leonor Correia 7
1 – Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa; 2 – Serviço de Medicina 2A, Hospital de Santa Maria, Centro Hospital Lisboa Norte; 3 – Serviço de Hematologia Clínica, Hospital S. Francisco Xavier, Centro Hospitalar Lisboa Ocidental; 4 – Serviço de Imunohemoterapia, Hospital S. Francisco Xavier, Centro Hospitalar Lisboa Ocidental; 5 – Unidade de Hematologia do Hospital Dona Estefânia, Centro Hospital Lisboa Central; 6 – Departamento de Promoção da Saúde, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa; 7 – Departamento de Bioquímica e Biologia Humana, Faculdade de Farmácia de Lisboa; Portugal
Iron-refractory iron-deficiency anaemia (IRIDA) is a rare disease characterized by severe hypochromic microcytic anemia, low serum iron and transferrin saturation, normal-high ferritin and inappropriate high levels of the hormone hepcidin. Patients are unresponsive to iron oral treatment and present a slow response to intravenous iron injections. The disease is caused by loss-of-function mutations in the TMPRSS6 gene, which protein is a negative regulator of hepcidin expression. In those patients, high hepcidin levels prevent iron absorption and recycling. Furthermore, it has been suggested that the gene common variants might modulate haematological phenotype and iron status.
Therefore, the aims of this work were to search for severe mutations in TMPRSS6 in order to elucidate some IRIDA-like phenotypes and to evaluate whether the SNP rs855791 influences iron deficiency anaemia (IDA) susceptibility in women.
Sequencing analyses of the TMPRSS6 gene were performed in 6 cases presenting IRIDA-like phenotypes. Additionally, the SNP rs855791 (p.V736A) was characterized in 25 women presenting IDA and in 89 women normal controls.
Molecular analyses of the IRIDA-suspected cases revealed the presence of a previously described mutation (p.K253E), a novel putative splicing variant and 3 other common variants. Concerning SNPs study, the frequency distribution of the rs8855791 genotypes showed a statistically association with women hemoglobin, serum iron level and transferrin saturation, being the proportion of CC homozygotes significantly lower in IDA patients.
Several degrees of iron deficiency anaemia can be attributed to genetic variants of TMPRSS6 gene and a relation genotype/phenotype can be established. Moreover, SNPs within the gene are able to modulate susceptibility to IDA. This suggests that TMPRSS6 has a role in iron-related common disorders in which it may act as a gene modifier.
Partially funded by FCT: PEst-OE/SAU/UI0009/2013 and PEst-OE/SAU/UI4013/2011