Role of VDR-genotype for immunological effects of vitamin D in liver cirrhosis

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Vitamin D has pleiotropic biological effects like modulation of innate and adaptive immune responses. Yet, vitamin D supplementation has no proven benefit on most clinical endpoints. However, subgroup analysis suggest that the benefit of vitamin D supplementation may depend on the individual VDR genotype. We could show a differential impact of calcitriol-analogs on the conformation of the VDR and consecutive gene transcription, though VDR genotype has not been considered in these investigations. We hypothesize, that individualized vitamin D therapy, taking into account the individual VDR genotype, may be more promising than vitamin D supplementation in the general population, and that calcitriol-analogs may be beneficial in individuals not responding to cholecalciferol/calcitriol. To test this hypothesis, a genetic association study shall be performed characterizing the outcome of liver cirrhosis as well as the immunophenotype of patients with liver cirrhosis in dependence of the VDR genotype. In ex vitro experiments, the impact of calcitriol-analogs on immune cells of these patients will be assessed in relationship to the genetic VDR background. Furthermore, an attempt will be made to identify the underlying causal genetic variant in the VDR. Collectively, these experiments shall result in a comprehensive understanding of the biological action of calcitriol and its analogs according to the individual genetic VDR background, which may provide a basis for further individualized vitamin D therapy in patients with liver cirrhosis.