Background: Leptin, initially recognized as a hormone regulating body weight and energy balance, has been shown to participate in diverse biological processes, including glucose metabolism, hematopoiesis, reproduction, and interactions with the immune system. The leptin receptor (LEPR), a class I cytokine receptor, plays a pivotal role in mediating these effects. Polymorphisms in the LEPR gene, particularly Q223R (rs1137101), have been linked to autoimmune diseases, type 2 diabetes, osteoporosis, and osteoarthritis (OA), suggesting its potential as a biomarker and therapeutic target.

Objectives: This study aimed to evaluate the association between the LEPR Q223R polymorphism and the risk of knee OA in a Ukrainian female population. Additionally, it examined the relationship between LEPR gene polymorphisms and clinical parameters such as body mass index (BMI), radiographic stages, and clinical forms of OA.

Methods: The study was approved by the ethics committee of the Vinnytsia National Medical University. A total of 199 female participants were recruited, including 99 knee OA patients and 100 healthy controls. Genomic DNA was extracted, and genotyping of the LEPR Q223R polymorphism was performed using allele-specific real-time polymerase chain reaction. Statistical analyses included the Student’s t-test, Fisher’s exact test, and logistic regression to assess the association between genotypes and clinical parameters.

Results: The frequency of the variant G allele was significantly higher in OA patients compared to controls (54% vs. 44%; OR = 1.53, 95% CI: 1.03–2.27, p = 0.04). In the recessive genetic model, homozygous GG carriers exhibited a markedly increased risk of knee OA (OR = 2.44, 95% CI: 1.28–4.65, p = 0.006). No significant associations were found between Q223R polymorphism and BMI across OA patients. However, a significant association was observed between disease duration (≥5 years) and radiographic severity in GG and AG genotype carriers (OR = 5.17, 95% CI: 1.04–25.57, p = 0.047). No significant relationship was detected between Q223R polymorphism and clinical forms of OA.

Conclusion: The LEPR Q223R polymorphism is significantly associated with knee OA susceptibility and disease severity in the Ukrainian female population. The findings highlight the potential role of LEPR as a biomarker for early diagnosis and targeted therapeutic strategies in OA. Further research is required to explore its clinical utility and the underlying mechanisms linking LEPR polymorphisms to OA pathogenesis.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.