AUTHOR=Zhao Kun , Nie Liuyan , Chin Grace Min Jun , Ye Xiangming , Sun Peng 

TITLE=Association between fat mass and obesity-related variant and osteoarthritis risk: Integrated meta-analysis with bioinformatics

JOURNAL=Frontiers in Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.1024750

DOI=10.3389/fmed.2022.1024750

ISSN=2296-858X

ABSTRACT=<sec><title>Objective</title><p>The association of fat mass and obesity-related (<italic>FTO</italic>) gene with osteoarthritis (OA) risk has been investigated in multiple genome-wide association studies but showed inconsistent results. Our study aimed to assess <italic>FTO</italic> expression in different OA sequencing datasets and to meta-analyze whether <italic>FTO</italic> polymorphism was associated with the risk of osteoarthritis.</p></sec><sec><title>Method</title><p>Gene expression profiles were obtained from ArrayExpress, Gene Expression Omnibus (GEO), and BioProject databases. Three electronic databases including PubMed and EMBASE were systematically retrieved to identify articles exploring the association between <italic>FTO</italic> polymorphisms and OA risk published before September 2022. Summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to perform the result. Stata software was utilized to conduct analyses on predetermined ethnicity and gender subgroups and sensitivity.</p></sec><sec><title>Results</title><p><italic>FTO</italic> gene was differentially expressed in the datasets from the UK. This systematic review and meta-analysis encompasses eight studies that revealed a significant association between <italic>FTO</italic> polymorphisms and OA risk [OR 1.07, 95% CI (1.03, 1.11), <italic>P</italic> &lt; 0.001] in the overall population. In subgroup analysis, a marked association was observed in European Caucasian [OR 1.08, 95% CI (1.04–1.12), <italic>P</italic> &lt; 0.001] and North American Caucasian with the Asian subgroups [OR 0.98, 95% CI (0.83–1. 6), <italic>P</italic> = 0.83] as an exception. Among the studies, four of them demonstrated attenuation in their OA risk after body mass index (BMI) adjustment in Caucasian populations.</p></sec><sec><title>Conclusion</title><p><italic>FTO</italic> significant differential expression was associated with the increased risk of OA in Caucasian populations. Nevertheless, the causality between <italic>FTO</italic> polymorphisms and OA risk remains largely elusive. Hence, further studies with larger sample size are necessary to validate whether <italic>FTO</italic> gene polymorphism contributes to OA susceptibility.</p></sec>