Vitamin D Receptor Polymorphisms Are Associated with 25(OH)D3 Concentrations and Systemic Inflammation in Decompensated Cirrhosis

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.