The Search for Idiopathic Scoliosis Genes

Ogilvie, James W.; Braun, John T.; Argyle, VeeAnn; Nelson, Lesa; Meade, Mary; Ward, Kenneth

doi:10.1097/01.brs.0000202527.25356.90

Cited by 107 publications

(58 citation statements)

References 10 publications

(6 reference statements)

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“…James W. Ogilvie and colleagues have identified genetic markers, two major genetic loci and 12 minor loci, related to the development of scoliosis [41]. They found 95% of patients with idiopathic curves greater than 40°had these genetic markers.…”

Section: Discussionmentioning

confidence: 99%

A History of Bracing for Idiopathic Scoliosis in North America

Fayssoux

Cho

Herman

2010

Clinical Orthopaedics &Amp; Related Research

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The care of the patient with scoliosis has a history extending back over two millennia with cast and brace treatment being a relatively recent endeavor, the modern era comprising just over half a century. Much of the previous literature provides a modest overview with emphasis on the history of the operative management. To better understand the current concepts of brace treatment of scoliosis, an appreciation of the history of bracing would be helpful. As such, we review the history of the treatment of scoliosis with an emphasis on modern brace treatment, primarily from a North American perspective. Our review utilizes consideration of historical texts as well as current treatises on the history of scoliosis and includes discussion of brace development with their proponents' rationale for why they work along with an appraisal of their clinical outcomes. We provide an overview of the current standards of care and the braces typically employed toward that standard including: the Milwaukee brace, the Wilmington brace, the Boston brace, the Charleston brace, the Providence brace and the SpineCor brace. Finally, we discuss future trends including improvements in methods of determining the critical period of peak growth velocity in children with scoliosis, the exciting promise of gene markers for progressive scoliosis and ''internal bracing'' options.

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Section: Discussionmentioning

confidence: 99%

A History of Bracing for Idiopathic Scoliosis in North America

Fayssoux

Cho

Herman

2010

Clinical Orthopaedics &Amp; Related Research

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“…The role of genetic factors in the development of AIS is widely accepted [25,26]. AIS is best understood as a complex phenotype that results from the interaction of multiple genetic loci with each other and the environment.…”

Section: Discussionmentioning

confidence: 99%

Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis

Qiu

Sun

et al. 2011

Eur Spine J

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Purpose To investigate whether the predisposition genes previously reported to be associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS) play a role in the effectiveness of brace treatment. Method A total of 312 AIS patients treated with bracing were enrolled in this study. The Cobb angle of the main curve was recorded at the beginning of brace treatment as well as at each follow-up. The patients were divided into two groups according to the outcome of brace treatment (success/failure). The failure of brace treatment was defined as a curve progression of more than 5°compared to the initial Cobb angle or surgical intervention because of curve progression. Single nucleotide polymorphism (SNP) sites in the genes for estrogen receptor a (ERa), estrogen receptor b (ERb), tryptophan hydroxylase 1 (TPH-1), melatonin receptor 1B (MTNR1B) and matrillin-1 (MATN1), which were previously identified to be predisposition genes for AIS, were selected for genotyping by the PCR-RFLP method. Differences of genotype and allele distribution between the two groups were compared by the v 2 test. A logistic regression analysis was used to figure out the independent predictors of the outcome of brace treatment. Results There were 90 cases (28.8%) in the failure group and 222 cases (71.2%) in the success group. Patients in the failure group were associated with the genotype GA (50.9 vs. 17.9% p \ 0.001) and the G allele (27.1 vs. 12.0%, p \ 0.001) at SNP rs9340799 of the ERa gene. Similarly, they were also associated with the genotype AT (33.3 vs.13.0%, p = 0.002) and the A allele (16.7 vs. 9.6%, p = 0.033) at SNP rs10488682 of the TPH-1 gene. For MTNR1B, the difference of genotype distribution between the two groups was found to be statistically significant, while the difference of allele distribution between the two groups was found to be marginally statistically significant; for the MATN1 and ERb genes, we found no significant differences of the genotype or allele distribution between the two groups. In the logistic regression analysis, ERa and TPH-1 were demonstrated to be independent factors predictive of bracing effectiveness. Conclusions ERa and TPH-1 might be potential genetic markers that could predict the outcome of brace treatment. Patients with the G allele at the rs9340799 site of the ERa gene and the A allele at the rs10488682 site of the TPH-1 gene are prone to be resistant to brace treatment.

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“…Clinical observations as well as population studies have documented scoliosis within families, with the prevalence higher among relatives than within the general population. 2,3 The mode of inheritance is still unclear, but evidence for autosomal dominant 4 X-linked inheritance 5 and multifactorial mode of inheritance has been described. 9 has been independently confirmed.…”

Section: Introductionmentioning

confidence: 99%

Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

et al. 2008

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Adolescent idiopathic scoliosis (AIS) is widely recognized as a complex disorder with a strong genetic predisposition. In previous studies, a number of extracellular matrixes (ECMs) related genes have been duplicated as candidate genes for AIS. Matrilin-1 plays an important role in the organization of the ECM, and matrilin-1 gene (MATN1) mutant mice showed similar phenotypes to scoliosis. We hypothesized that MATN1 was a candidate predisposition gene for AIS. A gene-based association study was conducted using seven tagging SNPs identified from the HapMap data. For initial screening, the seven tagSNPs were genotyped in 197 cases and 172 controls. Next, we validated any significant association in an additional sample of 222 cases and 288 controls. In addition, another 290 controls were genotyped to confirm the results. We found that allele G of rs1149048 was a significant predisposition allele of AIS (P ¼ 0.0007, odds ratio (OR) ¼ 1.35 within 95% confidence interval (CI) ¼ 1.14 -1.61), and individuals with genotype GG had a higher risk for AIS compared with AA þ AG (P ¼ 0.0001, OR ¼ 1.61 within 95% CI ¼ 1.25-2.08). Polymorphism of rs1149048 was also associated with curve severity in AIS patients. Also, a significantly higher maximum Cobb angle was found in patients with GG genotype (P ¼ 0.002). We concluded that the tagSNP rs1149048 polymorphism in the MATN1 promoter region was associated with both susceptibility and disease progression in AIS.

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The Search for Idiopathic Scoliosis Genes

Abstract: Nearly all (97%) AIS patients have familial origins. There appears to be at least one major gene, and the differences in penetrance and expressivity in two large unconnected pedigrees might suggest the presence of more than one gene.

Cited by 107 publications

References 10 publications

A History of Bracing for Idiopathic Scoliosis in North America

A History of Bracing for Idiopathic Scoliosis in North America

Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis

Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population

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