Background Congenital dislocation of the hip (CDH), which is one of the most common skeletal congenital anomalies, results from an abnormality of the seating of the femoral head in the acetabulum. Importance of misalignment of femoral head defines different phenotypes ranging from luxation to mild forms of acetabular dysplasia (AD). CDH is a multifactorial disease with a strong genetic component attested by ethnical predispositions and familial aggregation. Recently, several studies reported the association between functional polymorphism of the 5'-untranslated region of GDF5 (Growth/Differentiation Factor 5) and CDH, a region that have also been reported to be associated with osteoarthritis.
Objectives The main goal of our study was to assess whether GDF5 is associated with mild forms of AD in adult patients with hip osteoarthritis.
Methods 131 Caucasian patients from the KHOALA (Knee or Hip Osteoarthritis Long Term Assessment) cohort with hip osteoarthritis were included in this study. All patients met both American College of Rheumatology and Kellgren and Lawrence (≥2) criteria for osteoarthritis. Patients underwent a morphological evaluation at both hips, based on standard anteroposterior and lateral X-rays. The morphological parameters retained here were the acetabular depth, VCE and HTE angles. Cut-off values to define AD were: VCE angle ≤20 °, HTE angle >12 °, or acetabular depth <9 mm. All patients were genotyped for two tagSNPs: rs143384 (C/T) and rs143383 (C/T), using the TaqMan® method. Association between SNPs and abnormal morphological values was tested using EpiInfo v6.04. An analysis of variance (ANOVA) was conducted to compare mean values of morphological parameters among groups defined by the genotypes.
Results 45.8% (60/131) of patients had at least one morphological parameter consistent with AD. 29.8% (39/131) had abnormal HTE, 25.2% (33/131) had abnormal acetabular depth, and 17.6% (23/131) had abnormal VCE. The case-control study revealed a significant association between rs143383 variant and AD, when defined by insufficient acetabular depth. Individuals carrying CT genotype had a 5 fold higher prevalence of AD compared to those carrying CC genotype (95% CI: [0.95-35.63], p=0.030). Prevalence of AD was not significantly increased among patients carrying TT genotype (OR TT vs. CC =4.03, 95% CI: [0.72-29.33], p=0.138), whereas a significant association was observed under a dominant model (OR =4.57, 95% CI: 0.93-30.53], p=0.035). No significant association with out of range HTE and VCE values was observed. For each SNP, mean VCE, HTE, and acetabular depth values were compared among the three groups defined by their genotypes.For rs143383 variant, a significant difference in acetabular depth was observed among individuals presenting at least one morphological parameter consistent with AD (ANOVA: F =6.19, p=0.004 in the right hip and F =7.59, p=0.001 in the left hip).
Conclusions This study confirms the association between GDF5 polymorphisms and CDH. It is the first publication to report an association between GDF5 and adult AD in context of hip osteoarthritis. Our results suggest an association between rs143383 and insufficient acetabular depth that should be assessed in further studies.
Disclosure of Interest None declared
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