Departamento de Genética Humana
Contributions
Type: Publication Only
Background
Anaemia is a worldwide blood disorder affecting about one-quarter of the world's population. Iron-deficiency anaemia (IDA) is the most common type of anaemia and is caused by inadequate iron availability for haemoglobin synthesis. The disorder development can be attributed to nutritional factors, namely to an iron deficiency diet. However, genetic variants may also be involved. Genome-wide association studies have suggested that common variants in the liver-expressed TMPRSS6 gene might modulate haematological phenotype and iron status. This gene encodes for a membrane-bound serine protease, matriptase-2, that plays an essential role in down regulation hepcidin, the key regulator of iron homeostasis. One of the suggested genetic variant is the SNP rs855791 c.2207 C>T, p.Ala736Val.
Aims
The objective of this work was to evaluate whether the SNP rs855791 in TMPRSS6 gene may influence IDA susceptibility in Portuguese women.
Methods
The SNP rs855791 (c.2207 C>T, p.V736A) was characterized at DNA level, using an allele specific amplification approach, in 25 Portuguese women presenting IDA (mean age = 38 years) and in another 89 women without IDA, corresponding to the normal control group (mean age = 39 years).
Results
We have found that the frequency of the three genotypes at SNP rs855791 is different between the two groups of women. The CC genotype frequency (736A) is lower in the IDA group than in controls and, inversely, the TT genotype frequency (736V) is higher; (p=0.037). Also, the TT genotype is associated with low haemoglobin level (p=0.036), serum iron (p=0.009) and transferrin saturation (p=0.015).
Summary
The genotype TT at SNP rs855791 within the gene TMPRSS6 is associated with the lowest haemoglobin levels and serum iron parameters of the studied women. Moreover, it is more frequent in the IDA group. Therefore, we can conclude that this variant is a genetic risk factor to develop IDA, which corroborates results obtained by previous studies in other populations.
So, this study has revealed that the TMPRSS6 gene, besides its association with the rare iron deficiency iron refractory anaemia (IRIDA), has also an important role as genetic modifier of common iron-related disorders. The polymorphism p.Ala736Val effect is probably due to a partial impairment of matriptase-2 and, consequently, to an increased expression of hepcidin which perturbs iron absorption in the duodenum as well as iron recycling by macrophages.
Partially funded by FCT: PEst-OE/SAU/UI0009/2013 and Pest-OE/SAU/UI4013/2011
Keyword(s): Genetic modifiers, Genetic polymorphism, Iron deficiency anemia
Session topic: Publication Only
Type: Publication Only
Background
Anaemia is a worldwide blood disorder affecting about one-quarter of the world's population. Iron-deficiency anaemia (IDA) is the most common type of anaemia and is caused by inadequate iron availability for haemoglobin synthesis. The disorder development can be attributed to nutritional factors, namely to an iron deficiency diet. However, genetic variants may also be involved. Genome-wide association studies have suggested that common variants in the liver-expressed TMPRSS6 gene might modulate haematological phenotype and iron status. This gene encodes for a membrane-bound serine protease, matriptase-2, that plays an essential role in down regulation hepcidin, the key regulator of iron homeostasis. One of the suggested genetic variant is the SNP rs855791 c.2207 C>T, p.Ala736Val.
Aims
The objective of this work was to evaluate whether the SNP rs855791 in TMPRSS6 gene may influence IDA susceptibility in Portuguese women.
Methods
The SNP rs855791 (c.2207 C>T, p.V736A) was characterized at DNA level, using an allele specific amplification approach, in 25 Portuguese women presenting IDA (mean age = 38 years) and in another 89 women without IDA, corresponding to the normal control group (mean age = 39 years).
Results
We have found that the frequency of the three genotypes at SNP rs855791 is different between the two groups of women. The CC genotype frequency (736A) is lower in the IDA group than in controls and, inversely, the TT genotype frequency (736V) is higher; (p=0.037). Also, the TT genotype is associated with low haemoglobin level (p=0.036), serum iron (p=0.009) and transferrin saturation (p=0.015).
Summary
The genotype TT at SNP rs855791 within the gene TMPRSS6 is associated with the lowest haemoglobin levels and serum iron parameters of the studied women. Moreover, it is more frequent in the IDA group. Therefore, we can conclude that this variant is a genetic risk factor to develop IDA, which corroborates results obtained by previous studies in other populations.
So, this study has revealed that the TMPRSS6 gene, besides its association with the rare iron deficiency iron refractory anaemia (IRIDA), has also an important role as genetic modifier of common iron-related disorders. The polymorphism p.Ala736Val effect is probably due to a partial impairment of matriptase-2 and, consequently, to an increased expression of hepcidin which perturbs iron absorption in the duodenum as well as iron recycling by macrophages.
Partially funded by FCT: PEst-OE/SAU/UI0009/2013 and Pest-OE/SAU/UI4013/2011
Keyword(s): Genetic modifiers, Genetic polymorphism, Iron deficiency anemia
Session topic: Publication Only