|
|
发育性髋节发育不良相关基因的系统研究
|
Abstract:
发育性髋关节发育不良(Developmental Dysplasia of the Hip，简称DDH)是是一种涉及髋关节结构异常和功能障碍的疾病，然而其具体发病机制及原因仍不清楚。其发病特征在于以髋关节发育不良为基础，导致关节囊松弛，股骨近端继发畸形，在髋臼对股骨头覆盖不良的情况下，逐渐出现股骨头脱位或半脱位于髋臼之外的下肢畸形。髋臼变浅以至于对股骨头覆盖降低是DDH引发髋关节不稳定进而引发青少年和青年期骨关节炎的重要原因。遗传和环境因素在DDH的发病机制中起重要作用。其发病机制和易感性相关基因尚未阐明。我们评估了PubMed数据库中索引的各种遗传学研究。我们分析了纳入研究的基本信息，并总结了DDH相关的突变位点，动物模型实验，与DDH相关的表观遗传学变化。
Developmental Dysplasia of the Hip (DDH) is a disease that involves structural abnormalities and functional impairments of the hip joint. However, its specific pathogenesis and causes are still unclear. The characteristic of its onset is based on developmental dysplasia of the hip joint, leading to laxity of the joint capsule and secondary deformities of the proximal femur. In the case of poor coverage of the femoral head by the acetabulum, lower limb deformities gradually appear with dislocation or semi dislocation of the femoral head outside the acetabulum. The shallowness of the acetabulum to the extent of reduced coverage of the femoral head is an important cause of hip instability caused by DDH, leading to osteoarthritis in adolescents and youth. Genetic and environmental factors play important roles in the pathogenesis of DDH. The pathogenesis and susceptibility related genes have not yet been elucidated. We evaluated various genetic studies indexed in the PubMed database. We analyzed the basic information included in the study and summarized the mutation sites related to DDH, animal model experiments, and epigenetic changes related to DDH.
| [1] | Wei, Y.S., Li, D.H., Liu, W.L., et al. (2016) Altered Chondrocyte Apoptosis Status in Developmental Hip Dysplasia in Rabbits. Balkan Medical Journal, 33, 639-644. https://doi.org/10.5152/balkanmedj.2016.150557 |
| [2] | Bakarman, K., Alsiddiky, A.M., Zamzam, M., et al. (2023) Developmental Dysplasia of the Hip (DDH): Etiology, Diagnosis, and Management. Cureus, 15, e43207. https://doi.org/10.7759/cureus.43207 |
| [3] | Roof, M.A., Gibon, E., Rios-Ruíz, G., et al. (2021) Has There Been a Change in the Age of Presentation of Patients with DDH after the Implementation of a Dedicated Ultrasound-Screening Program? Journal of Pediatric Orthopaedics, 41, 433-436. https://doi.org/10.1097/BPO.0000000000001871 |
| [4] | Zamborsky, R., Kokavec, M., Harsanyi, S., et al. (2019) Developmental Dysplasia of Hip: Perspectives in Genetic Screening. Medical Sciences, 7, Article 59. https://doi.org/10.3390/medsci7040059 |
| [5] | Basit, S., Hannan, M.A. and Khoshhal, K.I. (2016) Developmental Dysplasia of the Hip: Usefulness of Next Generation Genomic Tools for Characterizing the Underlying Genes—A Mini Review. Clinical Genetics, 90, 16-20. https://doi.org/10.1111/cge.12755 |
| [6] | Li, L., Sun, K., Zhang, L., et al. (2013) Heritability and Sibling Recurrent Risk of Developmental Dysplasia of the Hip in Chinese Population. European Journal of Clinical Investigation, 43, 589-594. https://doi.org/10.1111/eci.12084 |
| [7] | Feldman, G.J., Parvizi, J., Levenstien, M., et al. (2013) Developmental Dysplasia of the Hip: Linkage Mapping and Whole Exome Sequencing Identify a Shared Variant in CX3CR1 in All Affected Members of a Large Multigeneration Family. Journal of Bone and Mineral Research, 28, 2540-2549. https://doi.org/10.1002/jbmr.1999 |
| [8] | Li, L., Wang, X., Zhao, Q., et al. (2017) CX3CR1 Polymorphisms Associated with an Increased Risk of Developmental Dysplasia of the Hip in Human. Journal of Orthopaedic Research, 35, 377-380. https://doi.org/10.1002/jor.23294 |
| [9] | Basit, S., Alharby, E., Albalawi, A.M., et al. (2018) Whole Genome SNP Genotyping in a Family Segregating Developmental Dysplasia of the Hip Detected Runs of Homozygosity on Chromosomes 15q13.3 and 19p13.2. Congenital Anomalies, 58, 56-61. https://doi.org/10.1111/cga.12235 |
| [10] | Gumus, E., Temiz, E., Sarikaya, B., et al. (2021) The Association between BMP-2, UQCC1 and CX3CR1 Polymorphisms and the Risk of Developmental Dysplasia of the Hip. Indian Journal of Orthopaedics, 55, 169-175. https://doi.org/10.1007/s43465-020-00235-y |
| [11] | Shi, D., Dai, J., Zhu, P., et al. (2011) Association of the D Repeat Polymorphism in the ASPN Gene with Developmental Dysplasia of the Hip: A Case-Control Study in Han Chinese. Arthritis Research & Therapy, 13, Article No. R27. https://doi.org/10.1186/ar3252 |
| [12] | Sekimoto, T., Ishii, M., Emi, M., et al. (2017) Copy Number Loss in the Region of the ASPN Gene in Patients with Acetabular Dysplasia: ASPN CNV in Acetabular Dysplasia. Bone & Joint Research, 6, 439-445. https://doi.org/10.1302/2046-3758.67.BJR-2016-0094.R1 |
| [13] | Feldman, G., Dalsey, C., Fertala, K., et al. (2010) The Otto Aufranc Award: Identification of a 4 Mb Region on Chromosome 17q21 Linked to Developmental Dysplasia of the Hip in One 18-Member, Multigeneration Family. Clinical Orthopaedics and Related Research, 468, 337-344. https://doi.org/10.1007/s11999-009-1073-6 |
| [14] | Zhao, L., Tian, W., Pan, H., et al. (2013) Variations of the COL1A1 Gene Promoter and the Relation to Developmental Dysplasia of the Hip. Genetic Testing and Molecular Biomarkers, 17, 840-843. https://doi.org/10.1089/gtmb.2013.0179 |
| [15] | Zhang, L., Xu, X., Chen, Y., et al. (2020) Mapping of Developmental Dysplasia of the Hip to Two Novel Regions at 8q23-q24 and 12p12. Experimental and Therapeutic Medicine, 19, 2799-2803. https://doi.org/10.3892/etm.2020.8513 |
| [16] | Tian, W., Zhao, L., Wang, J., et al. (2012) Association Analysis between HOXD9 Genes and the Development of Developmental Dysplasia of the Hip in Chinese Female Han Population. BMC Musculoskeletal Disorders, 13, Article No. 59. https://doi.org/10.1186/1471-2474-13-59 |
| [17] | Hao, Z., Dai, J., Shi, D., et al. (2014) Association of a Single Nucleotide Polymorphism in HOXB9 with Developmental Dysplasia of the Hip: A Case-Control Study. Journal of Orthopaedic Research, 32, 179-182. https://doi.org/10.1002/jor.22507 |
| [18] | Dai, J., Shi, D., Zhu, P., et al. (2008) Association of a Single Nucleotide Polymorphism in Growth Differentiate Factor 5 with Congenital Dysplasia of the Hip: A Case-Control Study. Arthritis Research & Therapy, 10, Article No. R126. https://doi.org/10.1186/ar2540 |
| [19] | Rouault, K., Scotet, V., Autret, S., et al. (2010) Evidence of Association between GDF5 Polymorphisms and Congenital Dislocation of the Hip in a Caucasian Population. Osteoarthritis Cartilage, 18, 1144-1149. https://doi.org/10.1016/j.joca.2010.05.018 |
| [20] | Hatzikotoulas, K., Roposch, A., Shah, K.M., et al. (2018) Genome-Wide Association Study of Developmental Dysplasia of the Hip Identifies an Association with GDF5. Communications Biology, 1, Article No. 56. https://doi.org/10.1038/s42003-018-0052-4 |
| [21] | Kiapour, A.M., Cao, J., Young, M., et al. (2018) The Role of Gdf5 Regulatory Regions in Development of Hip Morphology. PLOS ONE, 13, e0202785. https://doi.org/10.1371/journal.pone.0202785 |
| [22] | Sadat-Ali, M., Al-Habdan, I.M. and Bubshait, D.A. (2018) Genetic Influence in Developmental Dysplasia of the Hip in Saudi Arabian Children Due to GDF5 Polymorphism. Biochemical Genetics, 56, 618-626. https://doi.org/10.1007/s10528-018-9864-7 |
| [23] | Baghdadi, T., Nejadhosseinian, M., Shirkoohi, R., et al. (2019) DNA Hypermethylation of GDF5 in Developmental Dysplasia of the Hip (DDH). Molecular Genetics & Genomic Medicine, 7, e887. https://doi.org/10.1002/mgg3.887 |
| [24] | Feldman, G., Offemaria, A., Sawan, H., et al. (2017) A Murine Model for Developmental Dysplasia of the Hip: Ablation of CX3CR1 Affects Acetabular Morphology and Gait. Journal of Translational Medicine, 15, Article No. 233. https://doi.org/10.1186/s12967-017-1335-0 |
| [25] | Feldman, G., Kappes, D., Mookerjee-Basu, J., et al. (2019) Novel Mutation in Teneurin 3 Found to Co-Segregate in All Affecteds in a Multi-Generation Family with Developmental Dysplasia of the Hip. Journal of Orthopaedic Research, 37, 171-180. https://doi.org/10.1002/jor.24148 |
| [26] | Watson, C.M., Crinnion, L.A., Gleghorn, L., et al. (2015) Identification of a Mutation in the Ubiquitin-Fold Modifier 1-Specific Peptidase 2 Gene, UFSP2, in an Extended South African Family with Beukes Hip Dysplasia. South African Medical Journal, 105, 558-563. https://doi.org/10.7196/SAMJnew.7917 |
| [27] | Ji, X., Liu, T., Zhao, S., et al. (2020) WISP-2, an Upregulated Gene in Hip Cartilage from the DDH Model Rats, Induces Chondrocyte Apoptosis through PPARγ in Vitro. The FASEB Journal, 34, 4904-4917. https://doi.org/10.1096/fj.201901915R |
