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The exploration of the relationship between hyperuricemia, gout and vitamin D deficiency
Yingdong Han1, Xinxin Han1, He Zhao1
1Department of Family Medicine & Division of General Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China; Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Complex Severe and Rare Diseases (Peking Union Medical College Hospital), Beijing, China.
Abstract:
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. 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). 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 = .0123) and 25(OH)D. Sensitivity analysis and genetic risk scores approach confirmed the robustness and reliability of the above findings. 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.
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