Epigenetic Regulation of the Clinical Signs of Friedreich’s Disease

Abstract

Objectives. To study the methylation profile of the FXN gene and its influence on the formation of the clinical presentation of Friedreich’s disease (FD). Materials and methods. The promoter area and intron 1 of the FXN gene up to the GAA expansion (UP-GAA) and after the GAA expansion (DOWN-GAA) regions were studied in 17 patients with FD, with analysis of a total of 45 CpG sites. Results. Studies of genetic-epigenetic interactions identified correlations between the extent of methylation of a series of CpG sites in the UP-GAA and DOWN-GAA and the number of GAA repeats in both expanded alleles of the FXN gene in patients with FD. We also found a link between methylation and the presence of the extraneural signs of FD: cardiomyopathy was more likely to be present when the CpG site of the promoter region was hypermethylated, while impairments to carbohydrate metabolism were more common in hypomethylation of CpG sites in the DOWN-GAA area. Conclusions. The data obtained here provide evidence that epigenetic modifications of the FXN gene make a significant contribution to forming the clinical picture of FD.