Abstract
ObjectivesThe 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 methodsA 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.ResultsMean 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).ConclusionsOur results show that rs8044769 in the FTO gene might be involved in TMJOA.Clinical relevanceThe 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.
Highlights
The FTO gene, which encodes 2-oxoglutarate-dependent nucleic acid demethylase [1], has been reported as an obesity-associated gene [2, 3] and is expressed in many tissues, including the cerebral cortex, hypothalamus, pituitary, and muscle [4]
The FTO gene was the first gene to be cloned after the identification of a fused toe (Ft) mutation resulting in a 1.6 Mb deletion in mouse chromosome 8 [5, 6]; its function remains unknown
Whereas many studies conclude that the rs8044769 polymorphism affects OA through obesity [12, 13], some believe that this hypothesis is not sufficiently proven because of the difficulty in confirming the causal relationship between obesity and OA [14]
Summary
The FTO gene, which encodes 2-oxoglutarate-dependent nucleic acid demethylase [1], has been reported as an obesity-associated gene [2, 3] and is expressed in many tissues, including the cerebral cortex, hypothalamus, pituitary, and muscle [4]. The FTO gene has been attracting attention in the field of orthopedics as a risk gene for osteoarthritis (OA) [8,9,10,11], and a genome-wide association study by Zeggini et al reported that the C allele of an FTO SNP (rs8044769) was strongly associated with OA in females [12]. Their excellent discoveries that have powerful influence on the subsequent studies have undoubtedly provided a great understanding of OA. Due to the weak relationship between occlusal force and BMI [16], TMJ is minimally affected by body weight
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