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=0.0007, odds ratio (OR)=1.35 within 95% confidence interval (CI)=1.14–1.61), and individuals with genotype GG had a higher risk for AIS compared with AA+AG (P=0.0001, OR=1.61 within 95% CI=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=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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Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population.

Vertebral development is a dynamic and complicated process, and defects can be caused by a variety of influences. Spinal curvature with no known cause (idiopathic scoliosis) affects 2-3% of the human population. In order to understand the etiology and pathogenesis of complex human skeletal defects such as idiopathic scoliosis, multiple models must be used to study all of the factors affecting vertebral stability and deformity. Although fish and humans have many of the same types of offenses to vertebral integrity, they have been overlooked as a resource for study. The most common morphological deformity reported for fish are those that occur during the development of the spinal system, and as with humans, curvature is a common morphological consequence. Here we review spinal curvature in teleosts and suggest that they are an unexploited resource for understanding the basic elements of vertebral stability, deformity, development and genetics. Fish can be a value to vertebral research because they are tractable, have a diversity of non-induced vertebral deformities, and substantial genomic resources. Current animal models lack non-induced deformities and the experimental tractability necessary for genetic studies. The fact that fish are free of an appendicular skeleton should allow for analysis of basic spinal integrity without the biomechanical constraints observed in quadrupedal and bipedal models. To illustrate the point we review human idiopathic scoliosis and the potential contribution teleosts can make for the identification of causes, risk factors, and treatment options.

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Teleosts as models for human vertebral stability and deformity.

SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese

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SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese.

The aetiology of adolescent idiopathic scoliosis (AIS) is still unknown despite many years of research effort. Theories on AIS’s aetiology have included mechanical, hormonal, metabolic, neuromuscular, growth, and genetic abnormalities. Amongst these, some factors may be epiphenomena rather than the cause itself. Other factors may even contribute to curve progression, rather than curve initiation. Current views maintain that AIS is a multifactorial disease with genetic predisposing factors [Lowe et al. in J Bone Joint Surg [Am] 82:1157–1168, 2000]. With improvements in diagnostic methods, imaging and genomics, there has been considerable recent work on aetiology. This review aims to bring readers up-to-date with the latest developments in scoliosis research.

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Recent advances in the aetiology of adolescent idiopathic scoliosis

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.

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

Objective To investigate the association of estrogen receptor β gene polymorphisms with susceptibility to adolescent idiopathic scoliosis Methods This study included 102 patients with AIS and 100 healthy controls Height,menarche status,curve pattern,Cobb angle,and Risser sign in female patients were recorded Blood samples were taken from each subject by venipuncture Genomic DNA was extracted from peripheral blood leukocytes using standard phenol/chloroform extraction PCR products from amplification of genomic DNA from all individuals were analysed using SSCP Mutation analysis were carried out for the samples with aberrant SSCP profiles and the polymorphic loci were analyzed by RFLP The χ2 test was used to determine the significant difference in genotype distribution between patients with AIS and the controls Results The frequency of CC genotype of the extron "OK",AA of the extron 5 were significantly higher in patients than that in controls (P 005) The C and A alleles appeared to be overrepresented in patients compared with controls (P 005) Furthermore,the frequencies of CC and AA genotypes in female patients whose height was≥160 cm and Cobb angle ≥30° were higher than those whose height was 160 cm and Cobb angle 30° (P 005) Conclusions The sites of the extron "OK",extron 5 polymorphism of estrogen receptor geneβ may be associated with a susceptibility of AIS Furthermore,The sites of the extron "OK" and extron 5 polymorphism may be associated with the height and the curve severity of patients

Zhao Di

Papers

Association of estrogen receptorβ gene polymorphisms with susceptibility to adolescent idiopathic scoliosis