Characteristics of the heme catabolic pathway in mild unconjugated hyperbilirubinemia and their associations with inflammation and disease prevention

Autor(en)

Christine Mölzer, Marlies Wallner, Carina Kern, Anela Tosevska, Rene Zadnikar, Daniel Doberer, Rodrig Marculescu, Karl-Heinz Wagner

Abstrakt

Heme catabolism exerts physiological functions that impact health through depressing inflammation. Upon reactive pathway progression, as in Gilbert's Syndrome (GS; UGT1A1∗28 polymorphism), aggravated health effects have been determined. Based on lower inflammation and improved metabolic health reported for GS, inter-group differences in heme catabolism were explored. Therefore, a case-control study including 120 fasted, healthy, age-and gender matched subjects with/without GS, was conducted. Genetic expressions of HMOX-1 and BLVRA were measured. Additionally participants were genotyped for those polymorphisms that are known (UGT1A1∗28) or likely (HMOX-1 microsatellites) to impact bilirubinemia. Intracellular interleukins (IL-6, IL-1β, TNFα), circulatory C-reactive protein (CRP), serum amyloid A (SAA) and haptoglobin (Hpt) were analysed as inflammatory markers. To assess intracellular heme oxygenase 1 (HO-1) isolated PBMCs were used. In GS vs. C, inflammation markers were significantly decreased. This was supported by an altered heme catabolism, indirectly reflecting in elevated unconjugated bilirubin (UCB; main phenotypic feature of GS) and iron, decreased hemopexin (Hpx) and Hpt and in up-regulated biliverdin reductase (BLVRA) gene expressions. Moreover, HMOX (GT)

_n short alleles were non-significantly more prominent in female GS individuals. Herewith, we propose a concept to elucidate why GS individuals encounter lower inflammation, and are thus less prone to oxidative-stress mediated diseases.

Organisation(en)

Department für Ernährungswissenschaften

Externe Organisation(en)

Fachhochschule Joanneum, Medizinische Universität Wien, University of Aberdeen, University of California, Los Angeles, Medizinische Universität Innsbruck

Journal

Scientific Reports

Band

Anzahl der Seiten

ISSN

2045-2322

DOI

https://doi.org/10.1038/s41598-017-00933-y

Publikationsdatum

04-2017

Peer-reviewed

ÖFOS 2012

303012 Gesundheitswissenschaften

Schlagwörter

Sustainable Development Goals

SDG 3 – Gesundheit und Wohlergehen

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/6fd0fed8-df26-4cde-a5cd-700570f334a3