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

Abstract

ObjectiveThe 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.MethodGene 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.ResultsFTO 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.ConclusionFTO 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.

The rs1477196 SNP of the FTO Gene is Associated with Primary Knee Osteoarthritis in a Female Population from Northern Mexico

“…A recent meta-analysis has shown that FTO gene polymorphisms were significantly associated with the risk of OA in the Caucasian population. However, it is notable that the rs1477196 variant was not included in this meta-analysis 24 . Wang et al observed a significant interaction between rs8044769 FTO genotypes and BMI with the risk of KOA (p = 0.037) and a marginal interaction of the polymorphism with age (p = 0.062) 22 .…”

“…Other studies have found contradictory results for the association between the SNPs of the FTO gene and OA [21][22][23] . Recently, a meta-analysis described the association between the SNPs of the FTO gene and the risk for knee osteoarthritis (KOA) as significant, particularly in the European Caucasian and North American Caucasian populations 24 .…”

The causal association between body mass index and risk of gonarthrosis: A Mendelian randomization study

“…Observational studies lack the randomization of exposure factors, making it challenging to eliminate the in uence of confounding variables and reverse causality in the observed correlation. Traditional randomized clinical controlled trials, while methodologically sound, are often impractical for studying this particular relationship due to ethical considerations [20][21][22][23].…”