The Modulatory Effects of the Polymorphisms in GLA 5'-Untranslated Region Upon Gene Expression Are Cell-Type Specific.

ABSTRACT: Lysosomal α-galactosidase A (αGal) is the enzyme deficient in Fabry disease (FD). The 5'-untranslated region (5'UTR) of the αGal gene (GLA) shows a remarkable degree of variation with three common single nucleotide polymorphisms at nucleotide positions c.-30G>A, c.-12G>A and c.-10C>T. We have recently identified in young Portuguese stroke patients a fourth polymorphism, at c.-44C>T, co-segregating in cis with the c.-12A allele. In vivo, the c.-30A allele is associated with higher enzyme activity in plasma, whereas c.-10T is associated with moderately decreased enzyme activity in leucocytes. Limited data suggest that c.-44T might be associated with increased plasma αGal activity. We have used a luciferase reporter system to experimentally assess the relative modulatory effects on gene expre

SUBMITTER: Ferreira S 

PROVIDER: S-EPMC4484901 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature