That has proven to be the case for the GDF5 polymorphism rs143383, a risk factor for knee osteoarthritis and several other common conditions, including lumbar-disc degeneration and developmental dysplasia of the hip.
Given GDF5 involvement in hip development, and osteoarthritis (OA) and developmental hip dysplasia (DDH) risk, here we sought to assess the role(s) of GDF5 and its regulatory sequence on the development of hip morphology linked to injury risk.
With an objective to assess the presence of SNP rs143383 and the alleles in the GDF5 gene among patients with DDH, parents, and unaffected siblings, we undertook this case-controlled study.
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.
GDF5 is involved in synovial joint development, maintenance and repair, and the rs143383 C/T single nucleotide polymorphism (SNP) located in the 5'UTR of GDF5 is associated, at the genome-wide significance level, with osteoarthritis susceptibility, and with other musculoskeletal phenotypes including height, congenital hip dysplasia and Achilles tendinopathy.
Methylation analysis showed that the promoter of GDF5 in cartilage samples from DDH patients was hypermethylated in comparison to healthy controls (p = .001).
To further evaluate this possible association, in the present study, we examined the genetic association of rs726252 in PAPPA2 gene with sporadic DDH in Han Chinese population using case-control study, including 310 patients with sporadic DDH and 487 control subjects, and found a significant association between PAPPA2 and DDH.
The PAPP-A2 and IGF pathway-associated proteins may also be involved in the development of the rat's hip joint, which bring the foundation for further revealing the pathogenic mechanism of DDH.
The aim of this study was to investigate the insulin-like growth factor (IGF) expression and collagen synthesis as well as cartilage proliferation-related proteins in the case of abnormal expression of Pappa2 in mice to research the relationship between PAPP-A2 and the pathological changes of DDH.
Association of interleukin-6 and transforming growth factor-β1 gene polymorphisms with developmental hip dysplasia and severe adult hip osteoarthritis: a preliminary study.
Variants in the Type II collagen (COL2A1) and vitamin D receptor (VDR) genes have been associated with patients with osteoarthritis of the hip secondary to DDH, suggesting these genes could contribute to DDH.
The COL1A1 mutation produced the most severe phenotypic effects, whereas those in the COL1A2 gene, regardless of the location or effect, produced congenital hip dislocation and other joint instability that was sometimes very marked.
We detected three variations in the COL1A1 gene promoter in patients and first demonstrated that the higher rate of total variations of COL1A1 gene contributed to DDH in Chinese female children; thus, the COL1A1 gene is a new candidate gene for DDH disease.
Data suggest association between TGFB1rs1800470" genes_norm="7040">29 T → C transition (rs1800470) and IL6 -572G → C transversion (rs1800796) with DDH, and also a possibility of TGF-beta1 and IL-6 interaction in DDH pathogenesis.
The literature documents numerous private mutations in COL2A1 associated with diverse clinical phenotypes including bilateral hip dysplasia and premature osteoarthritis.
Follow-up with whole-exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co-segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis.
Acetabular dysplasia (AD) appears to be a multi-factorial disease, which may involve both genetic and environmental factors and whose pathogenesis remains obscure.