부산대학교 도서관

Objective: Congenital dislocation of the hip (CDH) is a multifactorial disease which involves genetic factors that are still unidentified. Recently, a functional polymorphism (rs143383) of the 5'-untranslated region of GDF5 (Growth/Differentiation Factor 5) - previously reported to be associated with osteoarthritis - has been associated with CDH in a Chinese population. The aim of our study was to determine whether GDF5, known to be involved in bone, joint and cartilage morphogenesis, is also associated with CDH in Caucasians.Design: We genotyped three tagSNPs (rs224334, rs143384, rs143383) in 239 cases and 239 controls from western Brittany (France) where CDH is frequent, and tested the association using both single-locus and haplotype-based approaches.Results: The most significant association was observed with rs143384. The T allele of this SNP was overrepresented in cases (65.9% vs 55.9%, P=0.002). Under a recessive model, carriers of the TT genotype had a 1.71-fold higher risk of developing CDH than carriers of the other genotypes (OR(TT vs CT+CC)=1.71, 95% CI: [1.18-2.48], P=0.005). At a nominal level, the association was also significant with rs143383 (OR(TT vs CT+CC)=1.52, 95% CI: [1.05-2.19], P=0.026). The haplotype carrying the susceptibility alleles of these SNPs was also more frequent in cases (65.9% vs 55.9%, OR=1.53, 95% CI: [1.18-1.98], P=0.002).Conclusion: This study reports, for the first time, the association between GDF5 polymorphisms and CDH in Caucasians, and points out another polymorphism of interest that requires further investigation. Reduction in GDF5 expression might lead to developmental deficiency of ligaments and capsule in hip joint, and therefore contribute to CDH pathogenesis.