title: UGT1A1 gene polymorphism as a potential factor inducing iron overload in the pathogenesis of type 1 hereditary hemochromatosis.
abstract: Aim Hereditary hemochromatosis is a common genetic disorder characterized by iron overload and subsequent organ damage. It is caused in most cases by HFE gene mutations which penetrance can be affected by many factors. The aim of this study was to establish the role of UGT1A1 gene polymorphism and serum bilirubin concentration in the pathogenesis of hereditary hemochromatosis. Methods Biochemical, histopathological and genetic data indicating iron excess and serum total bilirubin concentration were determined in 32 patients with the type 1 hereditary hemochromatosis. Fluorescent molecular probes assays were used for genotyping of UGT1A1*28 and UGT1A1*60 mutations in these individuals. Results High incidence and a significant correlation of UGT1A1 gene mutations with increased serum bilirubin level and lower grades of liver tissue inflammatory activity were observed in study participants. UGT1A1*28 and UGT1A1*60 mutations were strongly linked together. Two of the subjects presented very rare genotypes of UGT1A1 gene: (TA)(5/7) and c.-64G>C heterozygotes. Conclusions UGT1A1 gene polymorphism and as its consequence of high serum bilirubin level may promote iron accumulation in hemochromatosis patients by reducing the activity of inflammation. We proposed a possible mechanism of this interaction.
authors.affiliation: Molecular Diagnostics Division, Department of Biotechnology, Intercollegiate Faculty of Biotechnology of University of Gdansk and Medical University of Gdansk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Romanowski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sikorska
authors.forename: Krzysztof Piotr
authors.initials: KP
authors.lastname: Bielawski