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

Objective: The association of fat mass and obesity-related (FTO) gene with osteoarthritis (OA) risk has been investigated in multiple genome-wide association studies but showed inconsistent results. Our study aimed to assess FTO expression in different OA sequencing datasets and to meta-analyze whether FTO polymorphism was associated with the risk of osteoarthritis. Method: 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 FTO 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. Results: FTO 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 FTO polymorphisms and OA risk [OR 1.07, 95% CI (1.03, 1.11), P < 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), P < 0.001] and North American Caucasian with the Asian subgroups [OR 0.98, 95% CI (0.83-1. 6), P = 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. Conclusion: FTO significant differential expression was associated with the increased risk of OA in Caucasian populations. Nevertheless, the causality between FTO polymorphisms and OA risk remains largely elusive. Hence, further studies with larger sample size are necessary to validate whether FTO gene polymorphism contributes to OA susceptibility.

Automated summary

This study evaluated FTO gene expression in different OA sequencing datasets and performed a meta-analysis to assess the association between FTO polymorphism and OA risk. The results showed a significant association between FTO polymorphisms and increased OA risk in Caucasian populations. However, the causality between FTO polymorphisms and OA risk remains unclear, and further studies with larger sample sizes are needed to validate their contribution to OA susceptibility.