Fabry disease is a rare genetic disorder caused by mutations in the GLA gene, leading to
reduced or absent activity of the enzyme α-galactosidase A. As a result, glycosphingolipids
accumulate in cells, affecting multiple organ systems. Renal involvement, or Fabry
nephropathy, is a major complication of the disease, significantly impacting patients’ quality
of life and survival.
Despite advances in treatment and diagnostic methods, early detection and prediction of the
progression of Fabry nephropathy remain a challenge. Classical biochemical markers of
kidney function are insufficient for identifying early damage, and patients with the same
genetic mutation can experience highly variable disease progression, likely influenced by
yet unknown genetic and environmental factors.
The aim of this master’s thesis is to investigate the role of genetic polymorphisms in non
coding regions of genes in the development and progression of Fabry nephropathy. We
included 284 patients with Fabry disease, categorizing them according to the rate of decline
in estimated glomerular filtration rate (eGFR) into a group with stable kidney function and
a group with progressive nephropathy. We analyzed the presence of ten selected
polymorphisms in non-coding regions of genes involved in podocyte function, as podocytes
play a crucial role in maintaining glomerular barrier structure and function.
Genotyping was performed using quantitative PCR with TaqMan hydrolysis probes. The
results showed that the presence of certain genotypes significantly increased the risk of rapid
progression of Fabry nephropathy. The two most significant polymorphisms were identified
in the SHROOM3 gene, where the associated genotypes were linked to a higher risk of
accelerated nephropathy progression.
Our findings confirm that genetic polymorphisms in non-coding regions of podocyte-related
genes can contribute substantially to understanding the phenotypic variability of Fabry
disease. This knowledge could pave the way for a more personalized approach to patient
monitoring and treatment and enable earlier identification of individuals at higher risk for
disease progression.
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