AUTHOR=Fang Xi , Chen Cong , Wang Zhi-Xin , Zhao Yan , Jiang Ling-Qiong , Fang Yang , Zhang Ruo-Di , Pan Hai-Feng , Tao Sha-Sha 

TITLE=Serum DKK-1 level in ankylosing spondylitis: insights from meta-analysis and Mendelian randomization

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1193357

DOI=10.3389/fimmu.2023.1193357

ISSN=1664-3224

ABSTRACT=<sec><title>Objective</title><p>The purpose of this study was to precisely evaluate the serum Dickkopf-1 (DKK-1) level in patients with ankylosing spondylitis (AS) relative to that in normal controls and to test the causal relationship between DKK-1 and the risk of AS.</p></sec><sec><title>Methods</title><p>Embase, PubMed, Web of Science, WANFANG DATA, VIP, and China National Knowledge Infrastructure (CNKI) were comprehensively searched until July 2022 for pertinent studies. The pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated by the fixed or random-effect model. In Mendelian randomization (MR) analysis on the causal relationship between serum DKK-1 level and AS risk, the inverse variance weighting method (IVW), MR-Egger regression, weighted median method, and weighted pattern method were applied. Sensitivity analyses, including the horizontal pleiotropy test, heterogeneity test, and leave-one-out test, were also performed.</p></sec><sec><title>Results</title><p>The meta-analysis of 40 studies containing 2,371 AS patients and 1,633 healthy controls showed that there was no significant difference in DKK-1 serum level between AS patients and normal controls (pooled SMD=0.207, 95% <italic>CI</italic> =−0.418-0.832, <italic>P=</italic>0.516). The subgroup analysis of the CRP ≤ 10 mg/L group showed that AS patients had higher serum DKK-1 concentration than the healthy controls (SMD=2.267, 95% <italic>CI</italic> = 0.102-4.432, <italic>P</italic>=0.040). Similarly, MR analysis also demonstrated no significant association between DKK-1 serum level and AS (IVW <italic>OR</italic>=0.999, 95% <italic>CI</italic> = 0.989-1.008, <italic>P=</italic>0.800). All sensitivity analyses revealed consistent results.</p></sec><sec><title>Conclusions</title><p>There was no significant change in serum DKK-1 concentration between AS patients and healthy controls. In addition, no causal relationship exists between serum DKK-1 levels and AS risk.</p></sec>