Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis.

Even though a mutation in monogenic diseases leads to a "classic" manifestation, many disorders exhibit great clinical variability that could be due to modifying genes also called minor genes. Fabry disease (FD) is an X-linked inborn error resulting from the deficient or absent activity of alpha-galactosidase A (α-GAL) enzyme, that leads to deposits of globotriaosylceramide. With our proprietary software SNPclinic v.1.0, we analyzed 110 single nucleotide polymorphisms (SNPs) in the proximal promoter of 14 genes that could modify the FD phenotype FD. We found seven regulatory-SNP (rSNPs) in three genes (, and ) in five cell lines relevant to FD (Cardiac myocytes and fibroblasts, Astrocytes-cerebellar, endothelial cells and T helper cells 1-T1). Each SNP was confirmed as a true rSNP in public eQTL databases, and additional software suggested the prediction of variants. The two proposed rSNPs in , could explain components for the regulation of active B cells that influence the fibrosis process. The three predicted rSNPs in , could act in apoptosis-autophagy regulation. The two putative rSNPs in , putatively regulate chronic inflammation. The seven rSNPs described here could act to modulate Fabry's clinical phenotype so we propose that , and be considered minor genes in FD.