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Serum 25-Hydroxyvitamin D, Vitamin D-Related Variants, and Risk of Chronic Liver Disease
30 Pages Posted: 30 May 2024
More...Abstract
Background: Whether vitamin D is associated with chronic liver diseases and whether vitamin D-related variants modify these associations remain unclear.
Methods: Serum 25(OH)D concentrations of participants from UK Biobank were measured by chemiluminescent immunoassay at recruitment. Variants rs4588 and rs7041 determine the GC isoforms to estimate the binding affinity values of 25(OH)D to VDBP. Vitamin D receptor (VDR) activity was calculated by summing the number of related alleles for rs11568820, rs2228570, and rs1544410. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models.
Findings: During the prospective follow-up of 401,551 participants, 4,404 incident NAFLD, 1,989 incident cirrhosis and 480 incident liver cancer were documented. HRs (95% CIs) for serum 25(OH)D level of ≥ 50 nmol/L (vs. < 25 nmol/L) were 0·70 (0·63-0·77) for NAFLD (Ptrend = 1·37×10-14), 0·43 (0·38-0·49) for cirrhosis (Ptrend = 8·66×10-29) and 0·65 (0·48-0·87) for liver cancer (Ptrend = 0·010). There were interactions between 25(OH)D and VDR activity for hepatic fibrosis and cirrhosis (Pinteraction = 0·024) and portal hypertension (Pinteraction = 0·019), and GC isoforms for liver cancer (Pinteraction = 0·033).
Interpretation: Serum 25(OH)D is associated with lower incidence of NAFLD, cirrhosis and liver cancer, and participants with low VDR activity / low affinity GC isoforms may benefit more from sufficient 25(OH)D for prevention of hepatic fibrosis and cirrhosis and portal hypertension / liver cancer.
Funding: Young Top-notch Talent Cultivation Program of Hubei Province
Declaration of Interest: The authors declare no competing interests.
Ethical Approval: All participants agreed to be involved in this study and have their health followed up. This study had approval from the North West Multi-centre Research Ethics Committee (MREC).
Keywords: Keywords: 25-Hydroxyvitamin D, variants, NAFLD, cirrhosis, Liver cancer
Suggested Citation: Suggested Citation