The rs1558902 <i>FTO</i> Variant Is Associated with Body Mass Index but Not with Knee Osteoarthritis in a Mexican Mestizo Population

<b><i>Background:</i></b> Knee osteoarthritis (KOA) is a multifactorial degenerative joint disease and a leading cause of disability in older adults. Obesity is the most modifiable risk factor for KOA. Previous studies have suggested an association between polymorphisms in the <i>FTO</i> (fat mass and obesity associated) genes and KOA, potentially mediated by obesity. This study aimed to evaluate the association between the rs1558902 <i>FTO</i> genetic variant, obesity, and KOA in a northern Mexican Mestizo population. <b><i>Materials and Methods:</i></b> A total of 462 individuals were included in the study. Participants were classified into three groups: (i) a reference population (<i>n</i> = 189), (ii) individuals with primary KOA (<i>n</i> = 130), and (iii) non-KOA individuals (<i>n</i> = 143). The rs1558902 variant was genotyped using DNA microarray technology in the reference population and by real-time PCR in the KOA and non-KOA groups. Binary and multinomial regression analyses were performed. <b><i>Results:</i></b> The rs1558902 variant showed a significant association with obesity in the reference population under codominant (<i>p</i> = 0.012) and recessive (<i>p</i> = 0.008) genetic models. These associations remained statistically significant after adjustment for sex and age using multinomial logistic regression. In the codominant model, the association with an odds ratio (OR) of 6.884 (95% confidence interval [CI]: 1.470-32.225; <i>p</i> = 0.014), while in the recessive model, the OR was 7.429 (95% CI: 1.619-34.091; <i>p</i> = 0.010). However, no significant association was observed between rs1558902 and KOA. <b><i>Conclusions:</i></b> These findings confirm the association between the rs1558902 <i>FTO</i> variant and overweight/obesity in a northern Mexican Mestizo population, but not with KOA. Further research is needed to explore this association in the context of other genetic and clinical factors.