Serum Bilirubin Levels and Promoter Variations in HMOX1 and UGT1A1 Genes in Patients with Fabry Disease

Autor: Giulia Bortolussi, Libor Vítek, Aleš Linhart, Alena Jiraskova, Lenka Eremiášová, Vilém Danzig, Gabriela Dostálová, Lubor Goláň
Rok vydání: 2017
Předmět:
Zdroj: Oxidative Medicine and Cellular Longevity, Vol 2017 (2017)
ISSN: 1942-0994
1942-0900
DOI: 10.1155/2017/9478946
Popis: The aim of our study was to assess the possible relationships among heme oxygenase (HMOX), bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations, serum bilirubin levels, and Fabry disease (FD). The study included 56 patients with FD (M : F ratio = 0.65) and 185 healthy individuals. Complete standard laboratory and clinical work-up was performed on all subjects, together with the determination of total peroxyl radical-scavenging capacity. The (GT)n and (TA)n dinucleotide variations in the HMOX1 and UGT1A1 gene promoters, respectively, were determined by DNA fragment analysis. Compared to controls, patients with FD had substantially lower serum bilirubin levels (12.0 versus 8.85 μmol/L, p=0.003) and also total antioxidant capacity (p<0.05), which showed a close positive relationship with serum bilirubin levels (p=0.067) and the use of enzyme replacement therapy (p=0.036). There was no association between HMOX1 gene promoter polymorphism and manifestation of FD. However, the presence of the TA7 allele UGT1A1 gene promoter, responsible for higher systemic bilirubin levels, was associated with a twofold lower risk of manifestation of FD (OR = 0.51, 95% CI = 0.27–0.97, p=0.038). Markedly lower serum bilirubin levels in FD patients seem to be due to bilirubin consumption during increased oxidative stress, although UGT1A1 promoter gene polymorphism may modify the manifestation of FD as well.
Databáze: OpenAIRE
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