The etiology of DDH disease remains unknown, despite its prevalence. DDH is a complex disorder with both environmental and genetic causes. The primary finding of the present study, we establish the association between one tag SNP located at the promoter region of HOXD9 gene and the development of DDH in Chinese female population. But it cannot be identified that the A-A haplotype was significantly associated with the presence of DDH because of the extremely small and unstable set of data. Thus, the studies of large sample size and different populations as well as functional experiments were needed to confirm the association between HOXD9 gene and DDH developing. So far, we had a preliminary result to regard HOXD9 gene may be a candidate gene for DDH developing.
Hypothetically, genes or genomic polymorphisms which affect acetabular morphology and capsular laxity potentially relate to the development of DDH.
The function of Hox
genes at a later phase of limb development is less well defined but is likely to involve the regulation of cell differentiation. Hox
genes suppress chondrogenesis directly and indirectly in the limb bud [16
], which indicate that Hox
genes not only have a role in early patterning processes but are also important for bone cell differentiation.Thus, Hox
genes have an instructive role in determining the shape and ossification patterns of bones.
With regard to HOX9
paralogous genes and DDH developing, HOXB9
gene has been reported with contradictory results. In 2003, Jiang et al. firstly identified that HOXB9
gene may be a susceptibility gene of DDH [18
]. Rouault et al. reported in 2009 that there is no relationship between HOXB9
and DDH [19
]. Recently, a genome-wide screening of one 18-member, multigeneration family with DDH identified a linkage on a limited location of the specific chromosome 17q21 where HOXB9
gene located in [20
]. Besides, there has been no report on HOXD9
In chicken model, the earliest Abd-B-like Hoxd
gene expression bserved during limb bud outgrowth is the uniform activation of Hoxd9
along the entire anterior/posterior extent of the early limb bud [11
]. Where after, Hoxd11Hoxd12
are activated sequentially at the posterior border of the limb bud [11
In mouse, the importance of HoxD
genes for normal skeleton growth and patterning has been established through loss and gain of function experiments [16
]. Meanwhile, mutational analysis of some of these genes has demonstrated that they play an important role in limb development [21
According to the result of the present study, we speculated the mechanism between the relationship of HOXD9 gene and the development of DDH as follows:
Firstly, HOXD9 gene regulate muscle cell growth, proliferation, differentiation and innervation, it can be speculated that these gene abnormalities cause muscle denervation, resulting in muscular dystrophy, or muscle fiber type and quantity of muscle leads to the malformation.
Secondly, HOXD9 gene possibly induced the undifferentiated mesenchymal cells differentiate into cartilage and new bone via BMP gene family. Thus, this gene can affect the acetabular shape, the ossification groove development and the positioning of the femoral head.