Abstract
BACKGROUND/OBJECTIVES: Knee osteoarthritis (KOA) is a multifactorial and degenerative disease. Growth differentiation factor 5 (GDF5) polymorphism rs143384 G > A is associated with reduced gene expression and musculoskeletal pathologies. This study aimed to evaluate the association between this functional polymorphism and clinical variability and disease severity among patients with KOA in an admixed population. METHODS: This cross-sectional observational study enrolled 224 Brazilian patients with KOA, who were evaluated and classified according to disease severity. RESULTS: The median age was 64 (44-84) years; 75.9% of the patients were female, 50.9% were shorter than 1.60 m, and 67.4% were obese or morbidly obese. The disease severity distribution was 64.7% grades I-III and 35.3% IV-V. Patients with KOA who were over 70 years had significantly more advanced grades (OR = 9.3; 95% CI = 3.4-26), in either female group (OR = 8.2; 95% CI = 2.6-26). The minor allele frequency of the GDF5 rs143384 A variant was 41.7% in the overall KOA case group, increasing with disease severity (39.7% in grades I-III versus 45.6% in IV-V). After adjusting for the confounding factors (age and BMI) the GDF5 GA + AA genotype was significantly associated with higher KOA severity IV-V in female patients (OR = 2.5; 95% CI = 1.2-5.3). Additionally, the mean height of female KOA patients with the GDF5 GA + AA genotype (1.56 ± 0.07 m) was significantly shorter than that of patients with the GG genotype (1.59 ± 0.08 m). CONCLUSIONS: The GDF5 rs143384 polymorphism was associated with greater KOA severity and shorter stature in female patients. These results suggest that this variant may contribute to phenotypic variability in patients with knee osteoarthritis, helping to refine clinical characterization and stratification in this population, contributing to personalized diagnoses and guiding future changes in treatment guidelines for knee osteoarthritis.