An association of transferrin gene polymorphism and serum transferrin levels with age-related macular degeneration

Age-related macular degeneration (AMD) is a degenerative disease of the eye, triggered by the damage of the macular cells. In the Western world it is the most frequent cause of blindness in the elderly. Oxidative stress is proved to play a key role in AMD pathogenesis and since iron accumulation has been found in AMD maculas, it may accelerate the oxidative processes in this tissue. In the present work we investigated the association between four polymorphisms of the transferrin gene (rs8177178; rs8177179; rs4481157; rs1130459) and AMD in dependence on the transferrin protein and iron serum levels. We employed PCR-RFLP (polymerase chain reaction – restriction fragment length polymorphism) for genotype determination, ELISA assay for serum transferrin evaluation and colorimetric assay for measurement of iron concentration in the serum. We found that advanced age and AMD family history may be independent risk factors for AMD (1.02, p < 0.05 and 8.88, p < 0.001, respectively). At the rs4481157 site The GG genotype of the rs4481157 polymorphism decreased the risk of dry AMD (OR 0.50; p < 0.05), while the GA increased this risk (OR 1.07; p < 0.05). Moreover, the GA genotype of this polymorphism decreased the risk of progression to the wet form (OR 0.63; p < 0.05). The analysis of the gene-environment interactions showed that the rs4481157 polymorphism modulates the AMD risk among obese (BMI above 30) individuals. In the former smokers group we observed a moderate association between rs4481157 polymorphism and AMD risk while this association in current smokers was stronger. We found also that the serum level of transferrin was higher in the AMD group (p < 0.001) than in the control, but the total serum iron levels did not differ between both groups. We found that the serum transferrin was associated with the rs8177178 (p < 0.001) and rs4481157 (p < 0.01) polymorphisms, and the common variant (GG) of both sites was related to a lower level of transferrin. Presented data may contribute to the involvement of iron homeostasis in AMD risk.

► Disturbances in iron homeostasis may be involved in AMD pathogenesis.
► Serum transferrin level in AMD patients was higher than in controls.
►  Transferrin expression may be modulated by polymorphisms of its gene.
► The -576G>A polymorphism of the transferrin gene modulated dry AMD risk.
► The -576G>A polymorphism interacted with smoking and obesity in AMD risk.