Heritability and sibling recurrent risk of developmental dysplasia of the hip in Chinese population

Li, Lianyong; Sun, Keming; Zhang, Lijun; Zhao, Qun; Cheng, Xianzhong; Dang, Youting

doi:10.1111/eci.12084

Cited by 18 publications

(19 citation statements)

References 25 publications

(63 reference statements)

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“…Femoroacetabular impingement in the hip joint and perinatal mechanical factors, such as breech presentation and swaddling, were confirmed as mechanical factors . Genetic factors, especially related gene disorders of cartilage metabolism, could also give rise to occurrence of DDH . Therefore, we speculate that these two major aspects may explain our results in the present study.…”

Section: Discussionsupporting

confidence: 63%

Severe cartilage degeneration in patients with developmental dysplasia of the hip

et al. 2017

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Developmental dysplasia of the hip (DDH) is a developmental disorder that has long-term chronic pain and limited hip joint mobility as major pathological characteristics. This study aims to access the association between the development of DDH and cartilage metabolic disorders. Cartilage tissue samples were acquired from patients with DDH, osteoarthritis (OA) and femoral neck fracture. The proteoglycan level was evaluated by safranin O-fast green, toluidine blue and hematoxylin-eosin (HE) staining. The levels of collagen-II (Col-II), collagen-X (Col-X) and metal matrix proteinase-13 (MMP-13) were evaluated by immunohistochemistry (IHC) and Western blotting analysis. The morphologic evaluation of cartilage was conducted by transmission electron microscopy (TEM). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA level of aggrecan, Col-II, Col-X and MMP-13. The aggrecan level in the cartilage matrix was significantly decreased in DDH patients by safranin O-fast green and toluidine blue staining in comparison with that in the OA and control groups. In contrast with the OA group, the Col-II expression was reduced while the MMP-13 expression increased in DDH patients, as shown by IHC and Western blotting analysis. The collagenous fibrils in cartilage of DDH patients appeared significantly sparse and disordered in the TEM analysis. In DDH patients, the mRNA expression levels of Col-II and aggrecan were markedly reduced, while the mRNA expression of Col-X was markedly increased, compared with the OA patients. There is severe articular cartilage degeneration in DDH patients. This observation provides us with new insight into cartilage metabolic regulation in DDH. © 2017 IUBMB Life, 69(3):179-187, 2017.

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Section: Discussionsupporting

confidence: 63%

Severe cartilage degeneration in patients with developmental dysplasia of the hip

et al. 2017

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“…Previous studies examining the epidemiology of DDH within families using linkage approaches have demonstrated that heritable factors contribute between 50% and 85% of the total risk or liability of disease 3,26,27 , depending on population ancestry. Here, we used dense genome-wide genotyping data to estimate the heritable risk of DDH among unrelated individuals of UK European ancestry in the general English population.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of developmental dysplasia of the hip identifies an association with GDF5

et al. 2018

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Developmental dysplasia of the hip (DDH) is the most common skeletal developmental disease. However, its genetic architecture is poorly understood. We conduct the largest DDH genome-wide association study to date and replicate our findings in independent cohorts. We find the heritable component of DDH attributable to common genetic variants to be 55% and distributed equally across the autosomal and X-chromosomes. We identify replicating evidence for association between GDF5 promoter variation and DDH (rs143384, effect allele A, odds ratio 1.44, 95% confidence interval 1.34–1.56, P = 3.55 × 10−22). Gene-based analysis implicates GDF5 (P = 9.24 × 10−12), UQCC1 (P = 1.86 × 10−10), MMP24 (P = 3.18 × 10−9), RETSAT (P = 3.70 × 10−8) and PDRG1 (P = 1.06 × 10−7) in DDH susceptibility. We find shared genetic architecture between DDH and hip osteoarthritis, but no predictive power of osteoarthritis polygenic risk score on DDH status, underscoring the complex nature of the two traits. We report a scalable, time-efficient recruitment strategy and establish for the first time to our knowledge a robust DDH genetic association locus at GDF5.

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“…DDH occurs in between 1 and 20 live births per 1,000 worldwide 44 , and predisposing factors include family history, being a first born, female sex and breech birth 45,46 . Familial segregation studies 47,48 suggest that DDH has a multifactorial genetic basis, but statistical support for this theory varies across populations and countries 49 . For example, in a Chinese population, the recurrent risk of DDH in the siblings of affected individuals was approximately tenfold greater than in controls and had a heritability of ~85% 47 .…”

Section: Ortolani Testmentioning

confidence: 99%

“…Familial segregation studies 47,48 suggest that DDH has a multifactorial genetic basis, but statistical support for this theory varies across populations and countries 49 . For example, in a Chinese population, the recurrent risk of DDH in the siblings of affected individuals was approximately tenfold greater than in controls and had a heritability of ~85% 47 . By contrast, the frequency of CHD varies between different dog breeds, reaching a peak of ~75% in Golden Retrievers and Rottweilers 50 , and shows no sex predilection in most breeds; the exception is Polish Tatra Sheepdogs, in which the risk of CHD in females is greater than threefold the risk in males 41 .…”

Section: Ortolani Testmentioning

confidence: 99%

Spontaneous dog osteoarthritis — a One Medicine vision

et al. 2019

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| Osteoarthritis (OA) is a global disease that, despite extensive research, has limited treatment options. Pet dogs share both an environment and lifestyle attributes with their owners, and a growing awareness is developing in the public and among researchers that One Medicine, the mutual co-study of animals and humans, could be beneficial for both humans and dogs. To that end, this Review highlights research opportunities afforded by studying dogs with spontaneous OA , with a view to sharing this active area of veterinary research with new audiences. Similarities and differences between dog and human OA are examined, and the proposition is made that suitably aligned studies of spontaneous OA in dogs and humans, in particular hip and knee OA , could highlight new avenues of discovery. Developing cross-species collaborations will provide a wealth of research material and knowledge that is relevant to human OA and that cannot currently be obtained from rodent models or experimentally induced dog models of OA. Ultimately , this Review aims to raise awareness of spontaneous dog OA and to stimulate discussion regarding its exploration under the One Medicine initiative to improve the health and well-being of both species.

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Heritability and sibling recurrent risk of developmental dysplasia of the hip in Chinese population

Abstract: This study for the first time exhibits a high sibling recurrent risk and heritability for DDH in Asian population. It also shows there is a high probability to identify the underlying predisposition genes in future genetic study.

Cited by 18 publications

References 25 publications

Severe cartilage degeneration in patients with developmental dysplasia of the hip

Severe cartilage degeneration in patients with developmental dysplasia of the hip

Genome-wide association study of developmental dysplasia of the hip identifies an association with GDF5

Spontaneous dog osteoarthritis — a One Medicine vision

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