Severity Of Adolescent Idiopathic Scoliosis Research Articles

Evaluation of thoracic vertebrae rotation in patients with pectus excavatum

PurposeThe aim of our study was to evaluate thoracic vertebrae rotation in patients with pectus excavatum. Moreover, we wanted to assess the prevalence, the severity and relationship between pectus excavatum and adolescent idiopathic scoliosis (AIS). MethodsWe performed retrospective analysis of 82 preoperative chest CT in children with pectus excavatum performed between January 2008 and December 2011. For each patient Haller Index and Cobb angle was measured. To evaluate the severity of thoracic scoliosis we measured vertebral rotation for Th8 and for vertebra at the level of highest chest deformation using Aaro-Dahlborn method. ResultsFrom the group of 54 patients with pectus excavatum enrolled in the study AIS was diagnosed in 8 patients (14,81%). In patients with symmetric deformation, Th8 rotation was found in 21 patients; the rotation of the apical vertebra was found in 20 patients. In patients with asymmetric deformation Th8 rotation was found in 10 patients; the rotation of the apical vertebra was found in 8 patients. Conclusions1. We have confirmed the higher prevalence of pectus excavatum in boys; 2. We have found a significant relationship between pectus excavatum and adolescent idiopathic scoliosis; 3. We have shown that deformation of the anterior chest wall enforces rotation of the thoracic spine; 4. We haven't found the relationship between the severity of the chest deformity (HI measured) and severity of AIS (Cobb angle measured); 5. We have shown a significant association between HI measured and rotation of thoracic vertebra at the level of highest chest deformation (apical vertebra) in symmetric pectus excavatum.Level of evidence: Level IV, Diagnostic study.

Dipeptidyl Peptidase-4 and Adolescent Idiopathic Scoliosis: Expression in Osteoblasts

It has been proposed that girls with adolescent idiopathic scoliosis (AIS) tend to have a taller stature and a lower body mass index. Energy homeostasis, that is known to affect bone growth, could contribute to these characteristics. In circulation, dipeptidyl peptidase-4 (DPP-4) inactivates glucagon-like peptide-1 (GLP-1), an incretin that promotes insulin secretion and sensitivity. Our objectives were to investigate DPP-4 status in plasma and in osteoblasts of AIS subjects and controls and to evaluate the regulatory role of metabolic effectors on DPP-4 expression. DPP-4 activity was assessed in plasma of 113 girls and 62 age-matched controls. Osteoblasts were isolated from bone specimens of AIS patients and controls. Human cells were incubated with glucose, insulin, GLP-1 and butyrate. Gene and protein expressions were evaluated by RT-qPCR and Western blot. Our results showed 14% inferior plasma DPP-4 activity in AIS patients when compared to healthy controls (P = 0.0357). Similarly, osteoblasts derived from AIS subjects had lower DPP-4 gene and protein expression than controls by 90.5% and 57.1% respectively (P < 0.009). DPP-4 expression was regulated in a different manner in osteoblasts isolated from AIS participants compared to controls. Our results suggest a role for incretins in AIS development and severity.

Association between IGF1 gene single nucleotide polymorphism (rs5742612) and adolescent idiopathic scoliosis: a meta-analysis.

Insulin-like growth factor 1 (IGF1) gene single nucleotide polymorphism (rs5742612) has been associated with adolescent idiopathic scoliosis (AIS) in several studies with limited sample size and inconsistent outcomes. So we perform this meta-analysis to assess the precise association between IGF1 gene single nucleotide polymorphism (rs5742612) and AIS. We systematically searched Pubmed, Embase, Web of Science and Cochrane Library up to January 19, 2016 to obtain relevant studies using our research strategy. Four articles all belonging to case-control studies were included in our meta-analysis. A total of four studies containing 763 cases and 559 controls satisfied the inclusion criteria after judgment by two reviewers. No significant associations were detected between IGF1 gene single nucleotide polymorphism (rs5742612) and AIS (T vs. C, OR=1.10, 95% CI 0.91-1.34, p=0.32; TT vs. CC: OR=1.28, 95% CI 0.82-2.02, p=0.28; TC vs. CC: OR=1.29, 95% CI 0.82-2.06, p=0.27; TT/TC vs. CC: OR=1.28, 95% CI 0.83-1.98, p=0.27; TT vs. OR=1.06, 95% CI 0.82-1.36, p=0.66). IGF1 gene single nucleotide polymorphism (rs5742612) is not significant associated with susceptibility to AIS in either Asian or Caucasian populations. However, IGF1 gene rs5742612 may be associated with severity of AIS. Further studies with larger sample size and different population groups involving the relationship are required to confirm the potential association.

Correlation between severity of adolescent idiopathic scoliosis and pulmonary artery systolic pressure: a study of 338 patients.

Study of patients with adolescent idiopathic scoliosis. To examine the correlation between pulmonary arterial pressure and coronal Cobb angle of idiopathic scoliosis. A total of 338 patients (82.8% female) with idiopathic scoliosis (average age 15.6years; range 14-20years) were included. Preoperatively, the coronal Cobb angle of curvature and the apex location and direction were determined from radiographic records. Tricuspid regurgitation velocity (TRV) and inferior vena cava diameter were also measured using Doppler echocardiography. Pulmonary arterial systolic pressure (sPAP) was calculated from the TRV according to the modified Bernoulli equation and correlations between sPAP and the features of scoliosis were identified by statistical analysis. Among the 338 patients, there were 305 thoracic curves, 276 (90.5%) of which were right curves, and 265 thoracolumbar/lumbar curves. sPAP varied from 5.0 to 37.6mmHg. Pulmonary hypertension could not be excluded in the case of one patient. A mild correlation (Spearman test, correlation coefficient=0.187, P=0.001) between sPAP and coronal Cobb angle of the main thoracic (MT) curves was identified. Correlations between sPAP and the degree of other curves were not significant. Patients with sPAP >20mmHg also had larger thoracic curve angles (mean MT 42.16° vs. 52.45°; U test, P=0.002). There were no differences in sPAP levels between patients with right and left thoracic curves. A mild positive correlation was identified between sPAP and the coronal Cobb angle of the MT curves. There was no relationship between sPAP and the direction of the curvature.

Investigation of the 53 Markers in a DNA-Based Prognostic Test Revealing New Predisposition Genes for Adolescent Idiopathic Scoliosis.

A genetic association study of 53 single nucleotide polymorphisms (SNPs) with adolescent idiopathic scoliosis (AIS). To explore new predisposition genes of AIS in Chinese Han population SUMMARY OF BACKGROUND DATA.: A panel of 53 SNPs were reported to be associated with curve severity of AIS. However, there is still a lack of knowledge concerning the association of these SNPs with the susceptibility of AIS in the Chinese Han population. A gene-based association study was conducted by genotyping the 53 SNPs of a prognostic test. DNA samples of 990 female patients with AIS and 1188 age-matched healthy controls were analyzed using the polymerase chain reaction-based Invader assay. The χ test was carried out to compare the differences of genotype and allele distributions between patients with AIS and healthy controls. A total of 4 SNPs were found to present significant differences in allele or genotype frequencies between the 2 groups. Compared with normal controls, patients were found to have significantly higher allele G of rs12618119 and allele A of rs9945359. Besides, patients were found to have significantly lower allele T of rs4661748 and allele C of rs4782809 than the normal controls. BIN1, CDH13, SETBP1, and SPATA21 genes could be associated with the susceptibility of AIS. Four new predisposition genes of AIS were identified on the basis of a large-scale case-control study. Putting all these findings together, it suggests that AIS is a multifactorial disease possibly involving different pathways such as development of central neural system and bone formation. Further studies exploring more predisposition gene are essential to illustrate the etiology of AIS and to guide the prevention or prognosis of the disease. 3.

Rs11190870 is not associated with severity of adolescent idiopathic scoliosis in Japanese

Objective We previously conducted a genome-wide association study for AIS susceptibility in Japanese and identified a SNP, rs11190870 near the LBX1 gene on chromosome 10q24.1 that showed significant association. The association is replicated in other populations of different ethnicities. However, it is controversial whether rs11190870 is also associated with severity of the scoliosis curve in AIS. To examine whether rs11190870 is associated with curve severity of AIS in Japanese, we investigated the association using 2,191 (2,068 female and 123 male) subjects.

Predictors of spine deformity progression in adolescent idiopathic scoliosis: A systematic review with meta-analysis.

To evaluate published data on the predictors of progressive adolescent idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of evidence. (1) study design: randomized controlled clinical trials, prospective cohort studies and case series, retrospective comparative and none comparative studies; (2) participants: adolescents with AIS aged from 10 to 20 years; and (3) treatment: observation, bracing, and other. Ovid MEDLINE, Embase, the Cochrane Library, PubMed and patent data bases. All years through August 2014 were included. Data were collected that showed an association between the studied characteristics and the progression of AIS or the severity of the spine deformity. Odds ratio (OR), sensitivity, specificity, positive and negative predictive values were also collected. A meta-analysis was performed to evaluate the pooled OR and predictive values, if more than 1 study presented a result. The GRADE approach was applied to evaluate the level of evidence. The review included 25 studies. All studies showed statistically significant or borderline association between severity or progression of AIS with the following characteristics: (1) An increase of the Cobb angle or axial rotation during brace treatment; (2) decrease of the rib-vertebral angle at the apical level of the convex side during brace treatment; (3) initial Cobb angle severity (> 25(o)); (4) osteopenia; (5) patient age < 13 years at diagnosis; (6) premenarche status; (7) skeletal immaturity; (8) thoracic deformity; (9) brain stem vestibular dysfunction; and (10) multiple indices combining radiographic, demographic, and physiologic characteristics. Single nucleotide polymorphisms of the following genes: (1) calmodulin 1; (2) estrogen receptor 1; (3) tryptophan hydroxylase 1; (3) insulin-like growth factor 1; (5) neurotrophin 3; (6) interleukin-17 receptor C; (7) melatonin receptor 1B, and (8) ScoliScore test. Other predictors included: (1) impairment of melatonin signaling in osteoblasts and peripheral blood mononuclear cells (PBMC); (2) G-protein signaling dysfunction in PBMC; and (3) the level of platelet calmodulin. However, predictive values of all these findings were limited, and the levels of evidence were low. The pooled result of brace treatment outcomes demonstrated that around 27% of patents with AIS experienced exacerbation of the spine deformity during or after brace treatment, and 15% required surgical correction. However, the level of evidence is also low due to the limitations of the included studies. This review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria.

Association between the ESR1 -351A>G single nucleotide polymorphism (rs9340799) and adolescent idiopathic scoliosis: a systematic review and meta-analysis.

A single nucleotide polymorphism in the promoter region of the estrogen receptor alpha gene (ESR1), rs9340799, has been linked with adolescent idiopathic scoliosis (AIS) in several association studies with limited sample size and inconsistent findings. A systematic review can provide a comprehensive appraisal of literature evidence and a meta-analysis can obtain a more precise estimate of any association. The purpose of the present study was to assess and synthesize the currently available evidence on the association between rs9340799 and AIS by conducting a systematic review and meta-analysis. This review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed (MEDLINE), EMBASE, Scopus and HuGE Literature Finder databases were systematically searched to identify relevant studies following a sensitive strategy. Summary odds ratios and corresponding 95% confidence intervals (95 % CI) were estimated using the fixed-effect inverse variance model for allelic (G vs. A) and genotypic comparisons. Meta-analysis of four studies (n = 1,827 AIS cases and n = 1,253 controls) found a non-significant association between rs9340799 and AIS (allelic odds ratio 1.09, 95 % CI 0.96-1.23, p = 0.17). When examined in isolation, the rs9340799 polymorphism does not appear to be a likely susceptibility variant for AIS predisposition. However, rs9340799 may be associated with AIS severity, progression and treatment; further investigation is necessary to confirm these potential associations.

Lack of association between suppressor of cytokine signaling-3 gene polymorphism and susceptibility and curve severity of adolescent idiopathic scoliosis.

To explore whether the suppressor of cytokine signaling-3 (SOCS3) gene polymorphisms are associated with the susceptibility and abnormal growth pattern of adolescent idiopathic scoliosis (AIS). Three hundred and ninety eight AIS girls aged 10-18 years old were enrolled, and 367 age-matched healthy girls were recruited as controls. Only patients who had Cobb angles larger than 20º were included in this study. Anthropometric parameters including body weight, height, and body mass index (BMI) were measured for AIS girls. Rs4969198 was selected as tagSNP to cover all of the related polymorphisms on SOCS3. Genotyping was performed using PCR-based Invader assay with the probe sets designed and synthesized by third wave. The genotyping results were read with an ABI PRISM7900HT sequence detection system (Applied Biosystems, Foster City, CA). A subgroup of 322 skeletally mature AIS patients who did not received bracing or any other conservative treatment previously were analyzed to define the contribution of rs4969168 on curve severity, body height, body weight, and BMI. Rs4969198 was successfully genotyped. No significant difference of genotype frequencies from the Hardy-Weinberg equilibrium (HWE) test was noted for the AIS patients or the normal controls. Neither the genotype nor the allele frequencies of rs49691968 were significantly different between the AIS patients and the normal controls. Rs4969168 was not found to be associated with age, curve severity of scoliosis, and body height. AIS patients with AA genotype had significantly higher body weight and BMI than the patients with AG and GG genotype (P = 0.014). The SOCS3 gene polymorphisms are not associated with the occurrence of AIS, but the gene polymorphism (rs4969168) is associated with abnormal growth pattern of AIS, indicating that SOCS3 gene might be a disease-modifying gene of AIS.

A Comparison of the Somatometric Measurements of Adolescent Males With and Without Idiopathic Scoliosis

Prospective study comparing the somatometric measurements of young males with normal spinal curves and with adolescent idiopathic scoliosis (AIS) with respect to the severity of AIS. To assess the somatometric measurements of young males with normal spinal curves and with AIS using the conscription data. The progression of AIS is closely correlated with longitudinal growth during puberty. Although abnormal growth in female AIS patients has been well investigated, the growth of male AIS patients has not been well reported. During Korean conscription, 409 adolescent males with a normal spinal curvature and 420 adolescent males with AIS were enrolled. Those with AIS were grouped according to the severity of scoliosis using Cobb angles, according to the guidelines issued by the Korean military directorate. Group somatometric measurements, such as body height, corrected body height (corrected using Bjure's equation), body weight, and body mass index (BMI) were compared. Uncorrected heights were insignificantly different (P=0.234), but corrected heights, body weights, and BMIs were all significantly different between the normal and all AIS groups (P<0.001) (in AIS, corrected height was greater and body weight and BMIs corrected or uncorrected for height were lower). Cobb angles were not related to corrected body height or BMI, but was related to weight. Body weight was significantly less in the severe AIS group (Cobb angle >40 degrees) than in the mild or moderate AIS group (P<0.042). In Korean male AIS patients, significantly different somatometric results were observed: namely, a greater corrected height and a lower body weight and BMIs corrected or uncorrected for height. Furthermore, body weight was significantly lower in the severe group than in the moderate group. This study shows that abnormal growth is observed in male AIS patients and that body weight is closely correlated with AIS severity.

Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis susceptibility in a Han Chinese population

To investigate whether rs11190870 near LBX1 correlates with the susceptibility or curve progression of adolescent idiopathic scoliosis (AIS) in a Han Chinese population. A total of 949 AIS patients and 976 age-matched healthy controls were recruited. All the subjects were genotyped using the PCR-based invader assay. Case-control study and case-only study were performed to define the contribution of rs11190870 to predisposition and curve severity of AIS. Additionally, we further conducted a meta-analysis of the study findings together with those of previously reported studies. A significant association of rs11190870 with AIS was observed in the Han Chinese population (P = 1.8 × 10(-9); odd ratio = 1.51; 95 % confidence interval = 1.33-1.71), and AIS patients with TT genotype had a larger Cobb angle than those with TC or CC genotype (P = 0.005). The meta-analysis confirmed that the positive association of this SNP with AIS in the East Asian population. The SNP rs11190870 near LBX1 is associated with both susceptibility and curve progression of AIS.

A single-nucleotide polymorphism rs708567 in the IL-17RC gene is associated with a susceptibility to and the curve severity of adolescent idiopathic scoliosis in a Chinese Han population: a case-control study

BackgroundAlthough the pathogenesis of adolescent idiopathic scoliosis (AIS) remains controversial, genetic factors are thought to play key roles in the development of AIS. In a recent genome-wide association study, a polymorphism in the interleukin-17 receptor C (IL-17RC) gene was reported to be associated with the susceptibility to AIS, implicating IL-17RC as a novel predisposing gene for AIS. However, as this association has not been replicated in other populations, its global applicability remains unclear.MethodsA total of 529 Chinese girls with AIS and 512 healthy age-matched controls were recruited in this case–control study from June 2007 to December 2009. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the genotype of the single-nucleotide polymorphism (SNP) rs708567 in the IL-17RC gene. Case–control and case-only studies were performed to determine the association between the IL-17RC gene polymorphism and the susceptibility to and curve severity of AIS.ResultsThe GG genotype and G allele frequencies were significantly higher in the AIS patients than in the controls (χ2 test: P = 0.023 and 0.028, respectively). The risk for the GG genotype is 1.550-fold (95% CI: 1.062 - 2.261) higher than the AG genotype, and the risk for the G allele is 1.507-fold (95% CI: 1.046 - 2.172) higher than the A allele. Additionally, a subgroup of skeletally mature AIS patients (n = 241) who carried the GG genotype showed a significantly higher mean maximum Cobb angle than those carrying the AG genotype (36.01 ± 13.12° vs. 28.92 ± 7.43°, P = 0.007).ConclusionsThis study confirms the significant association between the IL-17RC gene polymorphism and the susceptibility to and curve severity of AIS in a Chinese Han population, suggesting that the IL-17RC gene is an AIS-predisposing gene in Chinese Han population.

A Promoter Polymorphism of Tissue Inhibitor of Metalloproteinase-2 Gene Is Associated With Severity of Thoracic Adolescent Idiopathic Scoliosis

A genetic association study of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene with adolescent idiopathic scoliosis (AIS) in a Chinese population. To determine whether a promoter polymorphism of the TIMP-2 gene correlates with the occurrence and curve severity of AIS patients. Previous studies have suggested that genetic factors play an important role in the etiology of AIS. The relative anterior spinal column overgrowth due to abnormal endochondral ossification has been considered to be a significant factor in the etiopathogenesis of AIS. The specific role of matrix metalloproteases (MMPs) and their activity inhibitors, TIMPs, during endochondral ossification has been documented. The TIMP-2 is the major TIMP expressed during bone development and is located in one of the chromosomal regions linked to AIS. Therefore, the TIMP-2 gene is a potential candidate gene for AIS. This study included a total of 570 female AIS patients, who were divided into 2 groups according to curve patterns. Of them, 354 patients with right thoracic curve were in group A (326 cases with Lenke 1 type and 28 cases with Lenke 2 type), whereas 216 patients with a single lumbar curve were in group B (216 cases with Lenke 5 type). A total of 210 age-matched healthy girls were recruited as normal controls. One single-nucleotide polymorphism, -418G/C (rs8179090), in the promoter region was selected for the TIMP-2 gene. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism in each group. No significant differences of genotype and allele frequency distribution were found between AIS patients and normal controls either in group A or in group B. The frequency of C allele was significantly higher in patients with Cobb angle 40° or more than in those with Cobb angle less than 40° in group A (P < 0.05), while this difference was not noted in group B (P > 0.05). Among the patients who reached skeletal maturity without any interference of natural history, a significantly higher average maximum Cobb angle was found in patients with C allele than in those without C allele in group A (P < 0.05). However, in group B, the mean maximum Cobb angle was similar between patients with different genotypes in both cases with left-side curves and cases with right-side curves (P > 0.05). Furthermore, for the patients whose values of thoracic kyphosis were recorded, those with C allele had smaller average thoracic kyphosis than those without C allele in group A (P < 0.05). However, such significant difference was not observed in group B. The single-nucleotide polymorphism SNP-418G/C (rs8179090) in the promoter region of the TIMP-2 gene was not associated with the occurrence of AIS. However, it may predict curve severity of thoracic AIS. Hence, the TIMP-2 gene is a disease-modifier gene of thoracic AIS.

A Promoter Polymorphism of Neurotrophin 3 Gene Is Associated With Curve Severity and Bracing Effectiveness in Adolescent Idiopathic Scoliosis

A genetic association study to comprehensively investigate variations of neurotrophin 3 (NTF3) gene polymorphisms in a Chinese Han population. To explore whether the NTF3 gene polymorphisms are associated with the susceptibility, curve severity, or bracing effectiveness of adolescent idiopathic scoliosis (AIS). Scoliosis has developed in mice with NTF3 deficiency in previous studies. Increased expression of NTF3 mRNA was detected in the paravertebral muscle in AIS. Moreover, linkage study has defined a novel AIS locus on chromosome 12p while NTF3 gene is located exactly in this interval. All evidence indicates a potential role of NTF3 in the pathogenesis of AIS. As for brace treatment of AIS, continuous sensory stimulation caused by an orthosis could help awareness of body misalignment and trigger curve correction through postural reflex. While NTF3 gene is tightly associated with proprioceptive feedback mechanism to adjust postural control, we hypothesized NTF3 as a potential candidate gene associated with the bracing effectiveness. A total of 362 AIS patients and 377 age-matched healthy controls were recruited. Two single-nucleotide polymorphisms (SNPs) were selected on the basis of the Chinese data from the HapMap project, and genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism for each SNP, respectively. Case-control study and case-only study were performed to define the contribution of NTF3 gene polymorphisms to predisposition and disease severity of AIS. Another subgroup of 120 skeletally immature AIS patients who received continuous brace treatment for minimal 2 years was genotyped, and bracing effectiveness was assessed to determine its association with NTF3 gene polymorphisms. The genotype and allele frequency distribution were similar between AIS and normal control for these 2 SNPs (χ² test: P > 0.05). For SNP rs11063714 in the promoter region of NTF3 gene, AIS patients with AA genotype showed significantly lower mean maximum Cobb angle than the patients with AG or GG genotypes (analysis of variance: P = 0.008). In addition, skeletally immature bracing AIS patients with AA genotype possessed significantly higher successful ratio of brace treatment compared with GG genotype (χ² test: P = 0.043). For SNP rs1805149, no significant association with predisposition or curve severity was detected. The NTF3 gene polymorphisms are not associated with the occurrence of AIS, but the promoter polymorphism (rs11063714) is associated with the curve severity, implicating an alleviating role of NTF3 in the curve progression of AIS. In addition, the promoter polymorphism is also associated with brace responsiveness. These findings indicated that NTF3 gene might be a disease-modifying gene of AIS.

Genomic polymorphisms of G-Protein Estrogen Receptor 1 are associated with severity of adolescent idiopathic scoliosis

Adolescent idiopathic scoliosis (AIS) is reported to be associated with the two traditional estrogen receptor genes, ESR1 and ESR2. Yet, the novel estrogen receptor G protein-coupled estrogen receptor 1 (GPER) has not been studied. To investigate the association of GPER gene polymorphisms with the onset and deterioration of AIS, we performed a case-control study. Clinical information was recorded, blood samples were taken and genomic DNA was extracted. After resequencing the gene in 45 cases and 45 controls who were randomly selected, 16 tag single nucleotide polymorphisms (SNPs) were selected. Then the association study was extended by an additional 344 patients and 293 controls with direct sequencing and a TaqMan-based genotyping assay. The chi-square test and logistic regression were used to analyse the genotypic and allelic association. One-way analysis of variance was used to compare the mean maximum Cobb angles and ages with different genotypes in the case-only data set. No association was observed between the polymorphisms of the GPER gene and susceptibility to AIS. However, heterozygotes in three SNPs of the gene (rs3808351, rs10269151 and rs426655s3) were related significantly with the curve severity in AIS patients (P = 0.004, 0.048 and 0.028, respectively). Our results demonstrate that GPER gene polymorphisms are associated with the severity of curvature in AIS; deficits of GPER may contribute to the deterioration of spine deformity.

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

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. 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 α (ERα), estrogen receptor β (ERβ), 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 χ(2) test. A logistic regression analysis was used to figure out the independent predictors of the outcome of brace treatment. 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 ERα 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 ERβ genes, we found no significant differences of the genotype or allele distribution between the two groups. In the logistic regression analysis, ERα and TPH-1 were demonstrated to be independent factors predictive of bracing effectiveness. ERα 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 ERα gene and the A allele at the rs10488682 site of the TPH-1 gene are prone to be resistant to brace treatment.

Time-to-contact and multiscale entropy identify differences in postural control in adolescent idiopathic scoliosis

Previous reports on changes in postural control in adolescent idiopathic scoliosis (AIS) compared to healthy controls have been inconsistent. This may suggest center of pressure (COP) sway parameters are not sufficient for determining the ability to maintain quiet upright stance indicating more complex measures may be needed to examine postural control in AIS. The purpose of this investigation was to compare postural control between AIS of different severity levels and healthy controls using time-to-contact (TtC), the complexity index of multiscale entropy (Cr), and COP sway parameters. Thirty-six AIS patients were classified as pre-bracing or pre-operative and compared to 10 healthy control subjects. Overall, the AIS patients showed significantly greater COP sway in mediolateral direction, but deficits with respect to the anteroposterior direction were only systematically identified with the time-to-contact and entropy measures. The multiscale entropy (Cr) results indicate that those with AIS utilize a different control strategy from healthy controls in the mediolateral direction that is more constrained, less complex and less adaptable. AIS severity further reduced this adaptability in the anteroposterior direction. These results indicate it is necessary to examine both planes of motion when investigating postural control in AIS. Additionally, the application of the measures used to assess the nature of the postural control changes in AIS should also be considered.

Association study of HTR1A and HTR1B with adolescent idiopathic scoliosis

To assess whether HTR1A and HTR1B polymorphisms are associated with the predisposition, gender, PUMC Classification and/or severity of adolescent idiopathic scoliosis (AIS). Rs6294 (HTR1A) and rs6296 (HTR1B) were genotyped in 103 AIS patients treated from January 2006 to March 2007, and 108 controls with matched gender and age. The data were analyzed by the allelic and genotypic association analysis, and the genotype-phenotype (gender, PUMC Classification, and Cobb angle) association analysis. The distributions of the alleles of all the 2 SNPs met Hardy-Weinberg equilibrium in the controls (goodness-of-fit chi(2) test, P > 0.05). The allele A of rs6294 was related with the occurrence of AIS (P = 0.041), but differences of the allele frequencies of rs6296 and the genotype frequencies of both SNPs between 2 groups had no statistical significance (P > 0.05). The genotype A/A + A/G of rs6294 was associated with AIS PUMC type III, and there was no other positive results in genotype-phenotype association analysis. These results suggest that HTR1A may be a predisposition gene of AIS PUMC type III, and PUMC Classification may has its genetic basis.

Repeatability, Reliability, and Concurrent Validity of the Scoliosis Research Society-22 Questionnaire and EuroQol in Patients With Adolescent Idiopathic Scoliosis

Cross-sectional study in patients with adolescent idiopathic scoliosis (AIS). To evaluate the repeatability, reliability, internal consistency, and concurrent validity (CD) of an adapted Norwegian version of the Scoliosis Research Society 22 questionnaire (SRS-22) and the generic health-related quality of life instrument EuroQol (EQ-5D and EQ-VAS). SRS-22 is widely used for evaluation of health-related quality of life in AIS. Its repeatability, which is essential for use in follow-up studies, and CD with EuroQol which can be used for cost-utility analysis, has not yet been assessed. The forward-backward translation of the English version of the SRS-22 was performed according to guidelines for cross-cultural adaptation of outcome questionnaires. Fifty-seven patients of various ages with AIS and deformity severity filled out standardized questionnaires: SRS-22, EQ-5D, and EQ-VAS, each twice in a 2-week interval. The study was approved by the Regional Ethics Committee for Medical Research in Norway. There were no floor or ceiling effects on the score distributions. The study demonstrated moderate internal consistency and high reliability of SRS-22 questionnaire with Chronbach alpha and intraclass correlation coefficiency ranging from 0.76 to 0.93 for the 5 domains. Repeatability was excellent for all SRS-22 domains with repeatability coefficients <1. CD with EQ-5D was poor to moderate with Pearson's r ranging from 0.14 to 0.58. However, total scores of the 2 instruments showed satisfactory agreement. The SRS-22 outcome instrument has satisfactory repeatability, but CD with EQ-5D suggests that the disease-specific and the generic questionnaire measure different constructs.

Association between insulin-like growth factor-1 receptor gene polymorphisms and with susceptibility to adolescent idiopathic scoliosis

To investigate the association of insulin-like growth factor-1 receptor (IGF-1R) gene polymorphisms and with susceptibility to adolescent idiopathic scoliosis (AIS). This study included 200 patients with AIS and 200 healthy controls. Height, menarche status, curve pattern, Cobb angle, and Risser sign in female patients were recorded. Blood samples were taken form each subject by venipuncture. Genetic DNA was extract from peripheral blood leukocytes using standard phenol/chloroform extraction. PCR-RFLP (polymerase chain reaction-restriction-fragment length polymorphism) was used for the genotyping. The genotype and allele frequency distribution were similar between AIS and normal control (P>0.05). The mean maximum Cobb angle, Risser sign, menarche status of different genotypes of IGF-1R gene were similar with each other among female AIS patients (P>0.05). The IGF-1R gene is neither associated with the occurrence nor the curve severity of AIS.