A novel missense variant in TXNDC3 is associated with developmental dysplasia of the hip in Han Chinese population.

Developmental dysplasia of the hip (DDH) is one of the most common inborn disabilities of the hip joint and a common disease with a genetic component for its etiology. However, genetic basis of Developmental dysplasia of the hip (DDH) remains largely unknown. Previous study has identified that TXNDC3 is significant associated with osteoarthritis and the development of chondrocytes and bone. In this study, we carried out a case-control study to investigate for the association between TXNDC3 and DDH, to find whether acetabular cartilage and bone formation in hip developmental progress is regulated by TXNDC3. We totally enrolled 984 radiology confirmed DDH children and 2043 healthy controls to conduct a case-control association study by genotyping SNP rs10250905 on TXNDC3. The rs10250905 variant is further detected in 7 DDH pedigrees which comprise total 15 familial DDH patients. The SNP was significantly associated with DDH, P = 1.53*10-5 with the odds ratio of 0.786 (0.705-0.877) for allele T; P = 0.0075 with the odds ratio of 0.761 (0.622-0.930) for genotype TT. Furthermore, the significant difference was also detected in samples when stratified by gender. In case-control study, the allele T frequency in cases (0.397) was lower than in controls (0.456). In addition, the allele T frequency in cases of DDH families was 0.300 and in controls was 0.433. In conclusion, our study demonstrates a novel missense variant of TXNDC3, rs10250905, is strongly associated with DDH in Han Chinese population and it shows protective allele T.