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. 2017 Apr 7;7:755. doi: 10.1038/s41598-017-00933-y

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Intracellular levels of interleukins are related to circulating UCB and underlying molecular measures of heme catabolism. Figure 4 shows explanatory powers of parameters that are involved in the heme catabolic pathway for variation in inflammatory markers. Inflammation appears to be directly influenced by UCB on the one hand, and by HMOX/BLVRA genetic expressions on the other. As far as UCB was concerned, a further connection with markers of inflammation was found that was mainly established through the variables of body composition (BMI, BF). Variation in the unspecific inflammatory marker of CRP is merely explained by the demographic variable age as well as body composition. The interconnection of iron and UCB emphasizes a potential feedback-loop of UCB on heme catabolism. Stepwise linear regression analysis was performed to assess inter-variable dependence and explanatory power (%), based on corrected R² values and a p-value of ≤0.05 (Supplementary Table S4). ^CEffect valid for control subjects only. Abbreviations: UCB: unconjugated bilirubin; UGT1A1: UGT1A1 genotype; IL-6/IL-1β: intracellular interleukins 6 and 1β; BLVRA expr.: genetic expression of biliverdin reductase; HMOX expr.: genetic expression of heme oxygenase; Hpt: haptoglobin; CRP: C-reactive protein; SAA: serum amyloid A.