Dataset Information

Evaluation of genetic susceptibility of common variants in SOX9 in patients with congenital talipes equinovarus in the Han Chinese population.

ABSTRACT: BACKGROUND:Congenital talipes equinovarus (CTEV) is a common birth defect that causes severe deformities of one or both feet. Genetics have been proven to play a key role in the risk of CTEV. Our study aimed to evaluate the genetic susceptibility of common variants in the SOX9 gene to CTEV in a Han Chinese population. METHODS:In this study, we recruited 2,205 study participants, including 692 CTEV patients and 1513 healthy controls. A total of seven selected single-nucleotide polymorphisms (SNPs) within the SOX9 gene were genotyped, and environmental variables, including maternal smoking and alcoholic drinking habits, were assessed. In addition, bioinformatics analyses were performed to explore the potential biological functions of the associated SNPs. RESULTS:The SNP rs73354570 was identified to be significantly associated with the risk of CTEV (OR = 1.53, P = 2.11 × 10-5), and the C allele was associated with an increased risk of CTEV. A dose-dependent pattern could be observed in genotypic analyses. The OR for individuals with AC genotypes was 1.37 (95% CI 1.09-1.71), and the OR for individuals with CC homozygotes was 1.47 (95% CI 1.18-1.82). Further analyses identified that rs73354570 is located within a region of multiple binding proteins, including CEBPB and POLR2A, which suggested that this SNP was also part of genetic motifs that are found within several cell types. CONCLUSION:Our results provide evidence supporting the important role of the SOX9 gene in the contribution to the risk of CTEV.

SUBMITTER: Li J

PROVIDER: S-EPMC7376870 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Evaluation of genetic susceptibility of common variants in SOX9 in patients with congenital talipes equinovarus in the Han Chinese population.

Li Jian J Wang Zhi Z Feng Dongxu D Wang Wei W Feng Weilou W

Journal of orthopaedic surgery and research 20200723 1

<h4>Background</h4>Congenital talipes equinovarus (CTEV) is a common birth defect that causes severe deformities of one or both feet. Genetics have been proven to play a key role in the risk of CTEV. Our study aimed to evaluate the genetic susceptibility of common variants in the SOX9 gene to CTEV in a Han Chinese population.<h4>Methods</h4>In this study, we recruited 2,205 study participants, including 692 CTEV patients and 1513 healthy controls. A total of seven selected single-nucleotide poly ...[more]

PMID: 32703248

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Project description:BACKGROUND:Treatment of idiopathic congenital talipes equinovarus (CTEV) is challenging for pediatric orthopedic surgeons. The Ponseti method is an effective protocol for treatment due to its technique of manipulation, casting, and limited surgery. Plaster casting is an essential component of the Ponseti method. In this report, we describe a new brace that was developed for use in the treatment of clubfoot in newborns instead of a plaster cast. METHODS:This retrospective study was performed in two orthopedic medical centers. Between January 2011 and October 2013, 89 newborns with CTEV (131?ft) underwent corrective treatment using fixation braces in the experiment group (E-group) in our hospital, and 107 newborns with CTEV (141?ft) underwent plaster casting in the control group (C-group) in another medical center. All patients were treated according to the Ponseti method after the application of the inclusion and exclusion criteria. Plaster casts were applied to patients in the C-group. The patients in the E-group received the custom-made polyaxial fixation braces instead of plaster casts. Prospective follow-up was performed for a mean duration of 36?months. The efficacy of the treatment was assessed using Pirani's scoring system. Chi-squared and independent t tests were used for statistical analyses. RESULTS:In the E-group, 85 patients (125?ft) achieved good appearance within 3?months of treatment initiation (average, 1.7?months). Four patients (6?ft) required percutaneous Achilles tenotomy. Seven patients developed sores during treatment because of improper brace application, but all sores healed without scarring with timely treatment. In the C-group, 96 patients (123?ft) achieved good appearance within 3?months of treatment initiation (average, 1.6?months). Eleven patients (18?ft) required percutaneous Achilles tenotomy. Twenty-one feet developed sores during treatment because of plaster cast pressure on the dorsum of the feet. Sixteen sores healed without scarring with timely treatment, and 5?ft had obvious scars. The overall mean Pirani scores 1 year after treatment were 0.26?±?0.06 in the E-group and 0.25?±?0.03 in the C-group, and the Pirani scores 3 years after treatment were 0.23?±?0.05 in the E-group and 0.22?±?0.03 in the C-group. There were significant differences in the percutaneous Achilles tenotomy and skin sores but no significant difference in the Pirani scores between these two groups. CONCLUSIONS:Our results showed that the new polyaxial fixation brace used in this study was an effective tool for the corrective treatment of CTEV in newborns. We propose the use of this brace as an alternative treatment for newborns.

Project description:BackgroundIdiopathic congenital talipes equinovarus (CTEV) is the commonest form of clubfoot. Its exact cause is unknown, although it is related to limb development. The aim of this study was to quantify the anatomy of the muscle, subcutaneous fat, tibia, fibula and arteries in the lower legs of teenagers and young adults with CTEV using 3D magnetic resonance imaging (MRI), and thus to investigate the anatomical differences between CTEV participants and controls.Methodology/principal findingsThe lower legs of six CTEV (2 bilateral, 4 unilateral) and five control young adults (age 12-28) were imaged using a 3T MRI Philips scanner. 5 of the CTEV participants had undergone soft-tissue and capsular release surgery. 3D T1-weighted and 3D magnetic resonance angiography (MRA) images were acquired. Segmentation software was used for volumetric, anatomical and image analysis. Kolmogorov-Smirnov tests were performed. The volumes of the lower affected leg, muscle, tibia and fibula in unilateral CTEV participants were consistently smaller compared to their contralateral unaffected leg, this was most pronounced in muscle. The proportion of muscle in affected CTEV legs was significantly reduced compared with control and unaffected CTEV legs, whilst proportion of muscular fat increased. No spatial abnormalities in the location or branching of arteries were detected, but hypoplastic anomalies were observed.Conclusions/significanceCombining 3D MRI and MRA is effective for quantitatively characterizing CTEV anatomy. Reduction in leg muscle volume appears to be a sensitive marker. Since 5/6 CTEV cases had soft-tissue surgery, further work is required to confirm that the treatment did not affect the MRI features observed. We propose that the proportion of muscle and intra-muscular fat within the lower leg could provide a valuable addition to current clinical CTEV classification. These measures could be useful for clinical care and guiding treatment pathways, as well as treatment research and clinical audit.

Project description:BackgroundPrevious studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data.MethodsWe obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore.ResultsWe included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10-8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10-16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum.LimitationsOur sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region.ConclusionWe found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.

Dataset Information

Evaluation of genetic susceptibility of common variants in SOX9 in patients with congenital talipes equinovarus in the Han Chinese population.

Publications

Evaluation of genetic susceptibility of common variants in SOX9 in patients with congenital talipes equinovarus in the Han Chinese population.

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