Involvement of an FTO gene polymorphism in the temporomandibular joint osteoarthritis

Abstract

Objectives The FTO gene has been reported as an obesity-associated gene and is also considered a risk gene for osteoarthritis (OA). However, its exact function is unclear, and there is conflicting evidence on the involvement of FTO polymorphisms in OA via obesity. The purpose of this study was to determine the effects of FTO polymorphism rs8044769 alleles on OA in the temporomandibular joint (TMJ), which is minimally affected by body weight. Materials and methods A total of 324 TMJs (113 with OA and 211 without OA, serving as controls) from 162 Japanese patients with temporomandibular disorders and undergoing MRI examination were analyzed. Genotyping was conducted, and multivariate analysis was performed after adjusting for the effects of age, sex, body mass index, and TMJ disc abnormalities. Results Mean age, BMI, and sex did not differ between the TMJs with OA and the TMJs without OA, but a significant difference was found for positional and dynamic disc abnormalities (P < 0.05). The allele frequency of FTO polymorphisms also differed significantly between the TMJs with OA and the TMJs without OA (P = 0.011). Moreover, logistic regression analysis showed no significant association between BMI (P = 0.581) and the occurrence of TMJOA but also indicated that the CC allele of rs8044769 is a risk factor for TMJOA (P = 0.040). Conclusions Our results show that rs8044769 in the FTO gene might be involved in TMJOA. Clinical relevance The present study provides a basis for a deeper understanding of the mechanism underlying degenerative skeletal diseases and the more effective selection and development of treatment strategies based on the patients’ genetic characteristics.

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

“…Panoutsopoulou et al examined the strength of association of rs8044769 with knee or hip OA (adjusted for gender) and detected a distinct association of the FTO variant with knee OA (OR 1.08 [95% CI 1.02-1.14], P = 0.009) rather than hip OA (OR 1.04 [95% CI 0.98-1.11], P = 0.17) in Caucasian populations. For nonweight-bearing joints such as hand and TMJ OA, FTO polymorphism also increased the OA risk (22,23). These findings require further validation in the future with larger-scale observational studies.…”

Regulatory Role of N6-Methyladenosine (m6A) Modification in Osteoarthritis

“…However, some argue that the causal relationship between obesity and OA is difficult to establish ( Pang et al, 2013 ), thus rejecting this theory. For example, compared patients with temporomandibular joint osteoarthritis (TMJOA)with the general population and concluded that the frequency of the FTO polymorphism allele was significantly different between the two groups, while the differences in weight, age, and sex were not statistically significant Takaoka et al (2022) . Yang et al found that lncRNA AC008 was highly expressed in human OA cartilage samples, and found that aberrant expression of AC008 affected OA progression by regulating chondrocyte viability, chondrocyte apoptosis and ECM degradation.…”

Causal association between body mass index and temporomandibular disorders: a bidirectional two-sample Mendelian randomization analysis

“…In vivo, the obese mice fed high-fat diets presented with osteoarthritis-like changes and increased the expression of Interleukin-1 Beta (IL-1B), Matrix metalloproteinase-3 (MMP-3) and leptin in temporomandibular joints [ 13 ]. Moreover, the CC allele of rs8044769 in the FTO gene (an obesity-associated gene) is proved as a risk factor for temporomandibular joint osteoarthritis [ 16 ]. Conversely, patients with TMDs might have difficulty in food intake and tend to lose weight [ 17 , 18 ].…”