Vitamin D Receptor Polymorphisms Are Associated with 25(OH)D3 Concentrations and Systemic Inflammation in Decompensated Cirrhosis
4 affiliations
- 1Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany
- 2Department of Internal Medicine II, LMU University Hospital, 81377 Munich, Germany
- 3Department for Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
- 4Institute for Pharmacogenetics, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
Abstract
Background/Objectives: Vitamin D regulates both the adaptive and the innate immune system, while having anti-inflammatory, immunomodulatory and anti-fibrotic properties. In clinical studies, 25(OH)D3 deficiency was associated with systemic inflammation, but it is unclear whether these associations are causal. In this study, we aimed to investigate the impact of Vitamin D receptor (VDR) polymorphisms (SNPs)—as surrogates for functional relationships—on 25(OH)D3 status and systemic inflammation in decompensated liver cirrhosis. Methods: Patients with compensated and decompensated cirrhosis with or without ACLF were enrolled prospectively from a monocentric cohort study (N = 355). Pyrosequencing was performed for genotyping SNPs (rs7968585, rs731236 (TaqI), rs7975232 (ApaI), rs2239179 and rs2228570 (FokI)). VDR-SNPs were analysed for their association with 25(OH)D3 concentrations and markers of systemic inflammation. Results: Severe 25(OH)D3 deficiency was frequent in decompensated cirrhosis. 25(OH)D3 supplementation was associated with significantly higher circulating 25(OH)D3 in compensated and decompensated liver cirrhosis, whereas in ACLF, 25(OH)D3 levels did not differ significantly between supplemented and unsupplemented patients. An inverse correlation of 25(OH)D3 and IL-6 levels was identified (R = −0.2286, 95% CI −0.328 to −0.124, p < 0.0001). In exploratory analyses among the analyzed VDR-SNPs, the GG-variant of rs2239179 was associated with lower 25(OH)D3 levels (β = 0.705, 95% CI 0.498-0.998, p = 0.049). Moreover, the functionally important VDR-SNP rs2228570 TC-variant showed a nominal independent association with higher IL-6 levels (ß = 1.685, 95% CI 1.102–2.576, p = 0.016) after adjustment. Conclusions: These exploratory findings suggest that VDR genetics may partially contribute to 25(OH)D3 status and systemic inflammation in liver cirrhosis and ACLF and warrant further replication in independent cohorts.
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BibTeX
@article{bauschen2026vitamin,
title = {{Vitamin D Receptor Polymorphisms Are Associated with 25(OH)D3 Concentrations and Systemic Inflammation in Decompensated Cirrhosis}},
author = {Alina Bauschen and Mona-May Langer and Helena Stadler and Nicholas Zeuzem and Birte Möhlendick and Sabrina Guckenbiehl and Christian M. Lange},
journal = {Nutrients},
year = {2026},
month = sep,
doi = {10.3390/nu18193234},
url = {https://europepmc.org/article/PMC/PMC13666896},
note = {CC BY},
}
RIS
TY - JOUR
TI - Vitamin D Receptor Polymorphisms Are Associated with 25(OH)D3 Concentrations and Systemic Inflammation in Decompensated Cirrhosis
AU - Alina Bauschen
AU - Mona-May Langer
AU - Helena Stadler
AU - Nicholas Zeuzem
AU - Birte Möhlendick
AU - Sabrina Guckenbiehl
AU - Christian M. Lange
PY - 2026
DA - 2026/09/30
JO - Nutrients
DO - 10.3390/nu18193234
UR - https://europepmc.org/article/PMC/PMC13666896
AB - Background/Objectives: Vitamin D regulates both the adaptive and the innate immune system, while having anti-inflammatory, immunomodulatory and anti-fibrotic properties. In clinical studies, 25(OH)D3 deficiency was associated with systemic inflammation, but it is unclear whether these associations are causal. In this study, we aimed to investigate the impact of Vitamin D receptor (VDR) polymorphisms (SNPs)—as surrogates for functional relationships—on 25(OH)D3 status and systemic inflammation in decompensated liver cirrhosis. Methods: Patients with compensated and decompensated cirrhosis with or without ACLF were enrolled prospectively from a monocentric cohort study (N = 355). Pyrosequencing was performed for genotyping SNPs (rs7968585, rs731236 (TaqI), rs7975232 (ApaI), rs2239179 and rs2228570 (FokI)). VDR-SNPs were analysed for their association with 25(OH)D3 concentrations and markers of systemic inflammation. Results: Severe 25(OH)D3 deficiency was frequent in decompensated cirrhosis. 25(OH)D3 supplementation was associated with significantly higher circulating 25(OH)D3 in compensated and decompensated liver cirrhosis, whereas in ACLF, 25(OH)D3 levels did not differ significantly between supplemented and unsupplemented patients. An inverse correlation of 25(OH)D3 and IL-6 levels was identified (R = −0.2286, 95% CI −0.328 to −0.124, p < 0.0001). In exploratory analyses among the analyzed VDR-SNPs, the GG-variant of rs2239179 was associated with lower 25(OH)D3 levels (β = 0.705, 95% CI 0.498-0.998, p = 0.049). Moreover, the functionally important VDR-SNP rs2228570 TC-variant showed a nominal independent association with higher IL-6 levels (ß = 1.685, 95% CI 1.102–2.576, p = 0.016) after adjustment. Conclusions: These exploratory findings suggest that VDR genetics may partially contribute to 25(OH)D3 status and systemic inflammation in liver cirrhosis and ACLF and warrant further replication in independent cohorts.
SN - 2072-6643
ER -