The exploration of the relationship between hyperuricemia, gout and Vitamin D deficiency.

Background: Our study aims to provide evidence concerning the relationship between hyperuricemia, gout and Vitamin D deficiency by analyzing data from Peking Union Medical College Hospital (PUMCH), the National Health and Nutrition Examination Survey (NHANES) database, and through Mendelian randomization (MR) analyses.

Methods: Sample 1 involved patients from PUMCH (n=13,532), and sample 2 involved participants from NHANES (Unweighted n=22,860; weight n=182,829,142). Logistic regression and restricted cubic spline analyses were applied to assess above relationship. A two-sample MR analysis was performed using the genome-wide association study summary statistics to identify the causal association between gout and 25-hydroxyvitamin D (25(OH)D).

Results: The results from both samples confirmed a positive correlation among hyperuricemia, gout and risk of Vitamin D deficiency. The restricted cubic spline showed positive dose-response relationship between uric acid and risk of Vitamin D deficiency and the minimal threshold of uric acid at 307.5 umol/L and 316.1 umol/L, respectively. Mediation analysis in the sample 2 found that about 29.4% of the total effect of gout on Vitamin D deficiency were mediated by serum uric acid, and 37.1% of which were mediated by body mass index.The results of our MR analysis supported a causal association between gout (IVW β(SE), -0.843 (0.337); P = 0.0123) and 25(OH)D. Sensitivity analysis and genetic risk scores approach confirmed the robustness and reliability of the above findings.

Conclusions: Hyperuricemia and gout are both strong indicators of increased risk of Vitamin D deficiency. Findings highlight the causal effects of gout-associated genetic variants on 25(OH)D.