To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

The g.1170C>T polymorphis… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

The g.1170C>T polymorphism of the 5' untranslated region of the human alpha-galactosidase gene is associated with decreased enzyme expression-Evidence from a family study.

Journal article
Authors JP Oliveira
S Ferreira
C Reguenga
F Carvalho
Jan-Eric Månsson
Published in Journal of inherited metabolic disease
Volume 31
Issue Suppl. 2
Pages 405–413
ISSN 1573-2665
Publication year 2008
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 405–413
Language en
Links dx.doi.org/10.1007/s10545-008-0972-...
Subject categories Medical and Health Sciences

Abstract

Subnormal leukocyte alpha-galactosidase (alpha-Gal) activity was found during evaluation of an adolescent male with cryptogenic cerebrovascular small-vessel disease. The only molecular abnormality found was the g.1170C>T single-nucleotide polymorphism (SNP) in the 5' untranslated region of exon 1 in the alpha-Gal gene (GLA). Historically, this polymorphism has been considered to be biologically neutral. To test the hypothesis that the g.1170T allele might be associated with lower alpha-Gal expression, we genotyped GLA exon 1 and measured leukocyte and plasma alpha-Gal in the parents, brother and sister of the index case. The g.1170T allele co-segregated with a subnormal leukocyte alpha-Gal activity in the three siblings. Although plasma enzyme activities were within the normal range in all five relatives, the ranking of their values suggested a dosage effect of the g.1170T allele. Western blotting assays of leukocyte protein extracts showed that the relative expression of alpha-Gal in both the patient and his sister was significantly lower than in sex-matched hemizygous or homozygous controls for the g.1170C allele, either normalized to the beta-actin immunoblot expression or standardized to a known amount of recombinant human alpha-Gal. These family data, in combination with results from a recent GLA SNP screening study among healthy Portuguese individuals, suggest that the g.1170C>T SNP may be co-dominantly associated with a relatively decreased GLA expression at the transcription and/or translation level. Larger population studies are needed to confirm these findings and to test the hypothesis that the GLA g.1170C>T may contribute to the multifactorial risk of ischaemic small-vessel cerebrovascular disease.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?