title: Characteristics of the heme catabolic pathway in mild unconjugated hyperbilirubinemia and their associations with inflammation and disease prevention.
abstract: 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)nshort 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.
authors.affiliation: University of Aberdeen, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, Foresterhill, Ashgrove Road West, AB25 2ZD, Aberdeen, UK. christine.moelzer@univie.ac.at.|University of Vienna, Faculty of Life Sciences, Department of Nutritional Sciences, Althanstraße 14 (UZA2), 1090, Vienna, Austria. christine.moelzer@univie.ac.at.
authors.forename: Christine
authors.initials: C
authors.lastname: Mölzer
authors.affiliation: University of Applied Sciences, FH JOANNEUM, Institute of Dietetics and Nutrition, Alte Poststraße, 149, 8020, Graz, Austria.
authors.forename: Marlies
authors.initials: M
authors.lastname: Wallner
authors.affiliation: Medical University of Vienna, Center for Physiology and Pharmacology, Institute of Pharmacology, Währingerstraße 13A, 1090, Vienna, Austria.
authors.forename: Carina
authors.identifier: http://orcid.org/0000-0003-1997-7527
authors.initials: C
authors.lastname: Kern
authors.affiliation: University of Vienna, Faculty of Life Sciences, Department of Nutritional Sciences, Althanstraße 14 (UZA2), 1090, Vienna, Austria.|Department of Molecular, Cell and Developmental Biology, UCLA, 610 Charles E. Young Drive East, Los Angeles, CA, 90095, USA.
authors.forename: Anela
authors.identifier: http://orcid.org/0000-0002-0892-7068
authors.initials: A
authors.lastname: Tosevska
authors.affiliation: Central Institute of Medical and Chemical Laboratory Diagnostics, University Clinics Innsbruck, 6020, Innsbruck, Austria.
authors.forename: René
authors.initials: R
authors.lastname: Zadnikar
authors.affiliation: Medical University of Vienna, Department of Clinical Pharmacology, Vienna General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Doberer
authors.affiliation: Medical University of Vienna, Clinical Institute of Laboratory Medicine, Vienna General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Rodrig
authors.initials: R
authors.lastname: Marculescu
authors.affiliation: University of Vienna, Faculty of Life Sciences, Department of Nutritional Sciences, Althanstraße 14 (UZA2), 1090, Vienna, Austria.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wagner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers; D016207:Cytokines / Q000097:blood; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006418:Heme / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D006932:Hyperbilirubinemia / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism* / Q000517:prevention & control; D007249:Inflammation / Q000209:etiology*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D018895:Microsatellite Repeats; D008875:Middle Aged; D012720:Severity of Illness Index; D012737:Sex Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D006418:Heme; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D001663:Bilirubin