The transferrin polymorphism: population genetics and associations with reproductive hazards and disease

Human serum transferrin (TF) carries iron from the intestine, reticuloendothelial system and liver parenchymal cells to proliferating cells in the body. TF is highly polymorphic, and previous findings of associations between TF types and reproductive hazards in different species suggest that the TF polymorphism may be involved in natural selection and susceptibility to disease. The aims of this thesis were: to examine the TF polymorphism in Finns, Swedes and Swedish Saamis and variations of TF allele frequencies between 23 North-Swedish subpopulations. to study TF types in relation to spontaneous abortion and disease. to investigate the relationship between TF types, iron-binding capacity and body iron stores in an attempt to elucidate the mechanism through which TF types may be involved in spontaneous abortion and disease. The following results were found: 1 Significant allele frequency differences were found between Finns, Swedes and Saamis. Finns had a lower TF*C2 frequency compared to Saamis and Swedes and the highest TF*C3 frequency so far observed in the world. Saamis had a very low TF*C3, and originally they probably lacked this allele. A significant heterogeneity between 23 subpopulations in northern Sweden was found for all TF alleles, and the geographical picture of TF*C3 and rare allele frequencies showed dines, which could be interpreted in terms of Finnish influence. 2 A significantly increased frequency of TF*C2 and especially the TF C2 type was found among mothers with a history of previous spontaneous abortion. 3 In patients with occupational photodermatosis of the face a highly significant increase of TF*C2 was found. 4 A highly significant association was found between TF*C3 and myocardial infarction. There was also an association with the TF C2 type, but with marginal significance. 5 In patients with hereditary hemochromatosis and thus extreme iron overload the frequency of TF*C1 was significantly increased, and this association was more pronounced in HLA-A3 associated hemochromatosis. 6 No significant relationship was found between TF types and serum iron, total iron binding capacity (TIBC), transferrin saturation and serum ferritin, thus the adverse effects of TF C2 and C3 appear to be independent of iron-binding and body iron stores.