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Background context As the biomechanical foundation of the spine, the pelvis was found to display rotation in the transverse plane in adolescent idiopathic scoliosis (AIS). However, the possible factors influencing the pelvic axial rotation (PAR) and its mechanism in patients with AIS remain unclear. Purpose To characterize the PAR in AIS patients with right major thoracic (MT) or major left thoracolumbar/lumbar (TL/L) curve and to explore the associated influencing factors and probable mechanism of compensation by analyzing the association between PAR and other spinal radiographic parameters. Study design Retrospective study. Patient sample All patients with the primary diagnosis of AIS from January 2008 to November 2009 were retrieved from our scoliosis database. Outcome measures Age, Cobb angle, and apex rotation of the main curve and the compensatory curve, curve flexibility, and PAR. Methods One-hundred thirty-two patients with right MT (14.7±1.8 years, 48±6.9°) and 83 patients with left major TL/L (14.7±1.5 years, 46±6.6°) were retrospectively reviewed. On standing full-spine posteroanterior radiographs, the PAR was quantified by the left/right hemi-pelvis width ratio (L/R ratio); then the subjects in both MT and major TL/L groups were divided into two subgroups: L/R ratio ≤1 (pelvis rotated to the right, R-PAR group); and L/R ratio >1 (pelvis rotated to the left, L-PAR group). Comparisons of all variables were performed between the L- and R-PAR subgroups; correlation and regression analysis were carried out to identify the influencing factors of PAR. Results The majority of the MT and major TL/L patients (75.8% vs. 60.2%) displayed right pelvic rotation, which was in the same direction as the thoracic curve. The incidence of R-PAR was greater in the MT patients than the major TL/L ones (p=.016). Lumbar flexibility in MT patients with R-PAR was greater than in MT patients with L-PAR (0.96±0.27 vs. 0.81±0.33, p=.038), which was contrary to the findings in the major TL/L patients (L-PAR>R-PAR, 0.79±0.15 vs. 0.70±0.22, p=.024). In the MT patients with R-PAR, the L/R ratio showed significant positive correlations with the lumbar Cobb angle (r=0.424) as well as with the apex rotation (r=0.488), which was further identified as an influencing factor (R=0.418) of the PAR. Significant positive correlations between L/R ratio and thoracic apex rotation (r=0.361) also were detected. Conclusion The majority of AIS patients with right MT or left major TL/L curves were found to have PAR to the right, in the same direction as the thoracic curve. The lumbar flexibility and apex rotation significantly influenced the PAR direction and magnitude. Moreover, the pelvis might be involved in compensation for the MT deformity through its connection with the lumbar spine.

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.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric skeletal disease. We previously reported a locus on chromosome 10q24.31 associated with AIS susceptibility in Japanese using a genome-wide association study (GWAS) consisting of 1,033 cases and 1,473 controls. To identify additional AIS-associated loci, we expanded the study by adding X-chromosome SNPs in the GWAS and increasing the size of the replication cohorts. Through a stepwise association study including 1,819 cases and 25,939 controls, we identified a new susceptibility locus on chromosome 6q24.1 in Japanese (P = 2.25 × 10(-10); odds ratio (OR) = 1.28). The most significantly associated SNP, rs6570507, was in GPR126 (encoding G protein-coupled receptor 126). Its association was replicated in Han Chinese and European-ancestry populations (combined P = 1.27 × 10(-14); OR = 1.27). GPR126 was highly expressed in cartilage, and the knockdown of gpr126 in zebrafish caused delayed ossification of the developing spine. Our results should provide insights into the etiology and pathogenesis of AIS.

The pelvis as the biomechanical foundation of spine, plays an important role in the balance of the stance and gait through the multi-link spinal-pelvic system. If the pelvic axial rotation (PAR) exists in adolescent idiopathic scoliosis (AIS) patients, it should theoretically have some effects on the body balance.To explore the probable effects of preoperative PAR on the spinal balance in coronal plane in AIS patients with main thoracolumbar/lumbar (TL/L) curve after posterior spinal instrumentation.Thirty-eight AIS patients (age: 15 ± 1.5 years) with main TL/L curve (51° ± 6.2°) were recruited retrospectively into this study. The mean follow-up period was 27 months (24-36 months). Standing full spine posteroanterior radiographs were taken preoperatively, 3 month and 1 year postoperatively, and at last follow-up. The convex/concave ratio (CV/CC ratio) of the anterior superior iliac spine laterally and the inferior ilium at the sacroiliac joint medially was measured on posteroanterior radiographs. According to the preoperative CV/CC ratios, the patients were divided into two groups: normal group (N-group: 0.95 ≤ CV/CC ≤ 1.05); and the asymmetrical group (A-group: CV/CC0.95, or1.05).In all the patients, the 3-month-postoperative CV/CC ratio (1.026 ± 0.087) was significantly different from the preoperative CV/CC ratio (0.969 ± 0.095, P0.001), indicating that the pelvis had rotated in the opposite direction of the corrective derotation load applied to the TL/L spine after surgery. No significant change was found in the CV/CC ratio from 3-month-postoperative to the last follow-up (1.013 ± 0.103, P0.05). There was no significant difference in the demographic, phenotypic, and treatment variables between the N- (n = 16) and A-groups (n = 22) (P0.05). However, more coronal decompensation occurred in the A-group after surgery (36.4 vs. 0.0 %, P = 0.013): two patients having trunk translation, three having lower instrumented vertebra (LIV) translation, and one having LIV tilt; meanwhile, one patient having both LIV translation and LIV tilt, and one having both trunk translation and LIV tilt.The present study confirmed the existence of PAR in AIS patients, and indicated that the pelvis would experience an active rebalancing in the transverse plane within 3 months after spinal correction, and since then, its position would remain stable. Moreover, TL/L-AIS patients with preoperative asymmetrical PAR probably had greater risk of coronal decompensation postoperatively.

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.

Study design A prospective clinical magnetic resonance imaging study. Objective To explore the differences in the position of the aorta relative to the spine in patients with single right thoracic adolescent idiopathic scoliosis (RT-AIS) in 2 different body positions (supine and prone). Summary of background data Pedicle screws are used widely in scoliosis surgery. With an increase in the incidence of vascular complications that result from misplaced pedicle screws, studies regarding the spatial relationship of the aorta and the vertebral body have also gradually increased and show that the aorta is positioned more posteriorly in patients with RT-AIS than in normal subjects. In these imaging studies, the patients received computed tomographic or magnetic resonance (MR) scans in the supine position. Recent studies of subjects without a spinal deformity found that the aorta moves from a posterolateral to an anteromedial position when the subject changes from a supine position to a prone position. However, no studies investigated aorta shifting with changing body position in patients with AIS. Methods Twenty-six patients with single RT-AIS were recruited into this study. Each patient received an axial MR scan from T5 through L3 in both the supine and prone positions. In the Cartesian coordinate system, the left pedicle-aorta (LtP-Ao) angle, LtP-Ao distance, and vertebral rotation angle were measured from T5 through L3 in the axial plane MR images. We also simulated misplacement of the pedicle screw with commonly used length and 20° direction error, and the potential risk of aorta impingement was defined as the virtual pedicle screw crossing the aorta. The paired sample t test was used to compare these parameters between the 2 body positions. Results The mean LtP-Ao angle and mean LtP-Ao distance differed between the body positions at each level. At the T5-T10 levels, the patients in the prone position exhibited significantly smaller LtP-Ao angles (26.2° vs. 38.8°; P, 0.01) and distances (27.0 vs. 30.7 mm; P, 0.01) than those in the supine position. The vertebral rotation angle was larger in the prone position than in the supine position at periapical levels, although this difference did not reach statistical significance (P . 0.05). The percentage of potential risk of aorta impingement was significantly higher in the prone position than in the supine position at the T5-T10 levels (19.7% vs. 6.6%, respectively; P, 0.05). CONCLUSION.: The aorta shifts more anteromedially and more closely to the spine at the T5-T10 levels when patients with RT-AIS change from the supine to the prone position. Thus, in the prone position, the aorta is potentially at a higher risk for injury from anterior and lateral cortex penetration by the left pedicle screws. The spinal surgeon should be aware of these altered conditions to avoid injury to the aorta during pedicle screw insertion in patients with RT-AIS who are in the prone position.

STUDY DESIGN An association study between radiologic measurements and cosmetic appearance in adolescent idiopathic scoliosis (AIS) patients with Lenke 5 and 6 curve types. OBJECTIVE The present study aimed at investigating the correlation between radiologic measurements and clinical cosmetic assessment indices in AIS with Lenke 5 and 6 curve types. SUMMARY OF BACKGROUND DATA Cosmetic truncal and pelvic distortions are of important concern to patients with AIS. In the clinical assessment of AIS, over reliance on radiologic evaluations without corresponding objective assessment of the external physical appearance is commonly practiced. Patients having the same radiologic findings could be quite different in their physical appearance and the reverse could also happen. These observations imply that discrepancies could well exist in the cosmetic versus radiologic evaluation in AIS. METHODS A total of 52 AIS patients with dominant lumbar/thoracolumbar curve including 36 Lenke type 5 and 16 Lenke type 6 were recruited. Cobb angles, coronal balance, thoracic containment, apical vertebral translation (AVT), pelvic oblique, apical vertebral rotation were measured in the standard long-standing posteroanterior radiographs. Waistline Height Index, Waistline Depth Index, Waistline Area Index, Waist Area Index, and hump index (α) were measured clinically and the 5 parameters combined into a composite cosmetic Index (CCI). Pearson rank correlation coefficient was used to assess measurement reliability for the cosmetic indices; correlation analysis and multiple linear regression analysis were made between the radiologic measurements and CCI. RESULTS The correlation coefficients between radiologic measurements and CCI ranged from -0.29 to 0.57, among which AVT was found to have the highest correlation coefficient, but not the Cobb angle. AVT, Cobb angle, coronal balance, thoracic containment were found to be significantly correlated with CCI (P < 0.05) with all correlation coefficients below 0.6. From linear regression analysis, CCI could be predicted by the equation (CCI = 98.0-1.18 x AVT-0.29 x Cobb angle) with adjusted R2 of 0.33 (implying that 33% of CCI variation could be accounted for by Cobb angle and AVT). CONCLUSION The present study showed that a number of radiologic indices could only partially reflect the objective cosmetic appearances in Lenke type 5 and 6 curves in AIS. Spine surgeons should put more emphasis in the clinical cosmetic evaluations and not relying solely on the radiologic assessment in AIS.

Shoulder balance is one of the key components to the body deformity in adolescent idiopathic scoliosis (AIS) patients with double thoracic curve and shoulder cosmesis plays an important role in patients' satisfaction of surgical outcomes. Up to now, only radiographic parameters were used to evaluate the shoulder balance in literatures; no corresponding cosmetic parameters have been developed to evaluate the cosmetic shoulder balance. Meanwhile, we often confronted that perfect radiographic shoulder balance was achieved, but the patients complained about the residual cosmetic deformity. This phenomenon implied that discrepancy may exist between radiographic shoulder balance and cosmetic shoulder balance. The present study was carried out to investigate the correlation between radiographic and clinical cosmetic shoulder balance in AIS patients with double thoracic curve. Thirty-four AIS patients were recruited for this study. All the patients had a double thoracic curve. Six cosmetic parameters--inner shoulder height (SHi), outer shoulder height (SHo), shoulder area index 1 (SAI1), shoulder area index 2 (SAI2), shoulder angle (alpha1) and axilla angle (alpha2) were developed and measured on the standing photographs. Also, seven radiographic parameters--T1 tilting (T1), first rib angle (FRA), clavicle angle (CA), coracoid process height (CPH), clavicle-rib cage intersection (CRCI), first rib-clavicle height (FRCH), trapezius length (TL) were measured on the standing posterior-anterior radiographs. Correlation analysis was made between cosmetic parameters and radiographic parameters. SHi was found to be significantly correlated with T1, FRA, CA, CPH, CRCI (P0.05), among which FRA had the highest correlation coefficient. SHo was found to be significantly correlated with T1, FRA, CA, CPH, CRCI, FRCH (P0.05), among which CRCI had the highest correlation coefficient. However, none of the correlation coefficient was greater than 0.8. The correlation coefficients between radiographic parameters and SAI1, SAI2, alpha1, alpha2 were also below 0.8 that were similar with SH. The results indicated that radiographic parameters could only partially reflect the shoulder cosmetic appearances. However, none of the existing parameters can accurately reflect the shoulder cosmetic appearance. As cosmesis is critical important to patients' satisfaction, spine surgeons should pay more attention to the cosmetic shoulder balance rather than radiographic shoulder balance.

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined=2.95 × 10−9), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined=7.59 × 10−13) and 18q21.33 near BCL-2 (rs4940576, Pcombined=2.22 × 10−12). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10−37), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS., The authors perform a genome-wide association study of adolescent idiopathic scoliosis patients of Han Chinese descent, and identify 3 new loci for disease susceptibility.

BACKGROUND In a recent genome wide association study, polymorphisms in the DSCAM and CNTNAP2 genes were reported to be related with susceptibility of AIS. Consequently, further replication studies are warranted in other populations due to ethnic difference in genetic background. OBJECTIVE To explore whether single nucleotide polymorphisms (SNPs) of DSCAM (rs2222973) and CNTNAP2 (rs11770843) genes are associated with the susceptibility and curve severity of AIS in a Chinese Han population. METHODS A total of 648 AIS patients and 573 age- and sex-matched healthy adolescents in rs2222973 were recruited, and in rs11770843 there were 100 AIS patients and 100 age- and sex-matched healthy adolescents included in present study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was repeatedly carried out to verify the linkage of AIS with SNPs rs2222973 in the DSCAM gene and rs11770843 in the CNTNAP2 gene. Case-control and case-only studies were respectively performed to define the contribution of the DSCAM gene polymorphisms to predisposition and disease severity of AIS. RESULTS Association analysis of the DSCAM SNP rs2222973 with AIS revealed no significant differences both in genotype frequency (p= 0.280) and allelic frequency (p= 0.643). The CNTNAP2 SNP rs11770843 (C/T) was not found in either the AIS or control group; all 100 AIS patients and 100 normal controls had the T/T genotype. Among skeletally matured AIS patients, the average maximal Cobb angles were also comparable within different DSCAM genotypes. CONCLUSION Our study did not repeatedly confirm the association of the rs2222973 or the rs11770843 with AIS in a Chinese Han population. We concluded that the associations of rs2222973 with AIS predisposition and curve severity are negative in a Chinese Han population.

Background A previous genome-wide association study (GWAS) suggested a strong association between the single nucleotide polymorphism (SNP) rs10510181 in the proximity of the gene encoding a cell adhesion molecule with homology to L1CAM (CHL1) and adolescent idiopathic scoliosis (AIS) in Caucasians. To clarify the role of CHL1 in the etiopathogenesis of AIS, we performed a case-control replication study in a Han Chinese population. Methods Five hundred female AIS patients between 10 and 18 years of age, as well as 500 age- and sex-matched controls were included. This study was conducted as a 2-stage case-control analysis: initial screening for the association between AIS and SNPs in and around the CHL1 gene (186 cases and 169 controls) followed by a confirmation test (314 cases and 331 controls). rs10510181 and 4 SNPs (rs2055314, rs331894, rs2272522, and rs2272524) in the CHL1 gene were selected for genotyping. Results Putative associations were shown between AIS and rs10510181, rs2055314, and rs2272522 in stage I. However, the associations were not confirmed in stage II. For rs10510181, the genotype frequencies were GG 28.8%, GA 46.2%, and AA 25.0% in AIS patients and GG 29.8%, GA 48.8%, and AA 21.4% in controls. No significant difference was found in genotype distribution between cases and controls (P = 0.39). Similarly, the genotype and allele distribution were comparable between case and control for rs2055314 and rs2272522. Conclusions There was no statistical association between polymorphisms of the CHL1 gene and idiopathic scoliosis in a Chinese population.

To investigate the effect of sympathectomy on the development and progression of scoliosis in bipedal C57BL/6J mice model.Sixty female 3-week-old C57BL/6J mice were selected to establish bipedal scoliotic mice model after amputations of forelimbs and tails. All mice were randomly divided into three groups, 20 mice for each group. Group 1 received daily intraperitoneal injection of 0.9% saline (5 mg/kg); while Group 2 and 3 received sympathectomy by daily intraperitoneal injection of propranolol (20 mg/kg) and guanethidine sulfate (40 mg/kg), respectively. Posteroanterior X-rays were obtained at 20th week. Curves were measured using Cobb method and scoliosis was defined as a Cobb angle of10°. Incidence of scoliosis and severity of curves were compared among groups using Chi-square test and One-way analysis of variance, respectively.There were 17 (85.0%) mice presented scoliosis in Group 1; whereas 11 (55.0%) and 10 (50.0%) mice presented scoliosis in Group 2 and 3, respectively. The incidence of scoliosis was found to be higher in Group 1, and the difference was statistically significant (χ(2) = 6.172, P = 0.046). As for curve magnitudes, the mean Cobb angle was 20° ± 9° in Group 1, 10° ± 7° in Group 2, and 12° ± 8° in Group 3. The mean Cobb angle of Group 1 was significantly greater than those of Group 2 and 3 (F = 9.545, P0.001), but there was no significant difference in mean Cobb angle between Group 2 and 3.Sympathetic nervous system may be involved in the development and progression of scoliosis in bipedal C57BL/6J mice model. Sympathectomy do not seem to dramatically decrease the incidence of scoliosis, probably due to that bipedalism itself may also be a cause of scoliosis in this animal model.

Study design A prospective magnetic resonance imaging (MRI) study. Objective The aim of this study was to quantitatively analyze the potential risks of aorta injury from thoracic pedicle screw (TPS) misplacement in right thoracic adolescent idiopathic scoliosis (RT-AIS) patients who are in the prone position. Summary of background data The aorta injuries are rare during posterior spinal surgery, but they can result in catastrophic complications when they do occur. However, we are aware of no prior studies that have used MRI images obtained with patients in the prone position for the purpose of systematically evaluating the potential risks of aorta injury due to TPS misplacement. Materials and methods This prospective study included 38 RT-AIS patients who underwent MRI scans in the prone position. We evaluated on the MRI images the aorta position relative to the scoliotic spine, and simulated placement of a left TPS with a lateral deviation different from the medium trajectory using Surgimap Spine imaging software. The maximum error of lateral direction was set to 10, 20, or 30 degrees (3 scenarios), and the length of the TPS was set at 30, 35, or 40 mm (3 scenarios). Sensitivity analysis was performed by variable direction errors and TPS lengths. The potential risk of aorta impingement was defined as the virtual TPS crossing the aorta. The percentages of potential risk of aorta impingement were calculated at each level in 9 scenarios. Results In the RT-AIS patients, the aorta shifted gradually from the left side of the vertebrae at midthoracic levels to a more anterior position at the lower thoracic levels, and was close to the vertebral body at T5-T6 and far away from the left cortex of vertebrae at T12. In 9 scenarios, with the increment of the lengths or/and direction errors of the simulated TPS, the risks of aorta impingement were consistently elevated at all the levels. The simulated 40 mm TPS at T5, T6, and T11 posed a higher potential risk of aorta injury (66%-74%) with a 30-degree lateral direction error. Conclusions Prone positioning may increase the potential risk of aorta injury in RT-AIS patients, particularly at T5-T6 and T11 even if a left TPS just barely touches the anteriolateral or lateral cortex of the vertebrae. Laterally misplaced TPSs should be removed at these high aorta-at-risk levels.

To study the relationship between T1 tilt and cosmetic shoulder balance in adolescent idiopathic scoliosis (AIS) patients.Seventy-one Lenke type 2 AIS patients were recruited into the present study from January 2010 to December 2011. There were 61 female and 10 male patients, the average age was (15.1 ± 2.9) years (range 10-18 years); the average Risser sign was 2.8 (range 1-5). The patients were photographed from the back in neutral standing position on level ground wearing underpants. Also, all the patients had a standing posterior-anterior radiograph in a relaxed standing position. The cosmetic shoulder height (CSH), which included cosmetic inner shoulder height (CSHi) and cosmetic outer shoulder height (CSHo), were measured in the photographs. Positive value was defined as left shoulder was higher than the right shoulder, and negative value was defined as right shoulder was higher than the left shoulder. CSH5 mm was defined as positive CSH, CSH-5 mm was defined as negative CSH, -5 mm ≤ CSH ≤ 5 mm was defined as leveled CSH. T1 tilts were measured in the posterior-anterior radiographs. Positive value was defined as the left proximal vertebral body up and right lower vertebral body down, and negative value was defined as the right proximal vertebral body up and left lower vertebral body down. T1 tilt5° was defined as positive T1 tilt, T1 tilt-5° was defined as negative T1 tilt, -5° ≤ T1 tilt ≤ 5° was defined as leveled T1 tilt.T1 tilt was found to be significantly correlated with CSHi and CSHo (r = 0.25 and 0.28, P0.05).For positive T1 tilt patients, there were 59.0% (36/61) patients with positive CSHo, 37.7% (23/61)with leveled CSHo, and 3.3% (2/61)with negative CSHo.For the patients with leveled T1 tilt, it was 3/10, 5/10 and 2/10.For positive T1 tilt patients, there were 83.6% (51/61) patients with positive CSHi, 11.5% (7/61) with leveled CSHi, and 4.9% (3/61) with negative CSHi; For the patients with leveled T1 tilt, it was 6/10, 2/10 and 2/10.Although positive correlation is found between T1 tilt and cosmetic shoulder balance, positive T1 tilt is not an indicator of higher left shoulder.Elevated left shoulder, leveled shoulders and elevated right shoulder are all found in positive T1 tilt patients.

To study the factors associated with postoperative shoulder balance in Lenke Type 1 adolescent idiopathic scoliosis (AIS) patients with preoperative right-elevated shoulder after posterior thoracic fusion.A total of 34 Lenke Type 1 AIS patients were recruited between October 2006 to October 2008. There were 8 boys and 26 girls with an average age of 15.1 years (range, 12 - 19 years). Posterior thoracic fusion was performed in all the patients. There were 23 cases proximally fused to T4 and 11 cases fused to T5. Pearson's correlation analysis was made between radiographic shoulder height (RSH) at the latest follow-up and preoperative T1 tilt, clavicle angle (CA), coracoids process height (CPH), apical vertebral translation (AVT), RSH, coronal and bending proximal/main thoracic curve (PT and MT) Cobb angle, curve flexibility as well as correction ratio of the MT curve.All patients presented right-elevated shoulder preoperatively, with an mean RSH of (-15.9 ± 5.8) mm. At the latest follow-up, PT curve correction was 44% ± 16%, and MT curve correction was 70% ± 10%. Of the 34 patients with an average postoperative RSH of (0.4 ± 7.9) mm, 32 patients had balanced shoulders, and only 2 patients had mild shoulder imbalance with left-elevated shoulder. The RSH at the latest follow-up was found to be negatively correlated with PT curve flexibility (r = -0.682, P0.01), but positively correlated with bending PT Cobb angle (r = 0.642, P0.01) and correction ratio of the MT curve (r = 0.557, P0.01). No significant correlations were found between RSH at the latest follow-up and preoperative T1 tilt, CA, CPH, AVT, RSH, coronal PT and MT Cobb angle, bending Cobb angle as well as flexibility of MT curve (P0.05).For the Lenke Type 1 AIS patients with preoperative right-elevated shoulder, proximal fusion to T4 or T5 could improve shoulder balance significantly. However, the low PT curve flexibility and overcorrection of MT curve may be associated with postoperative shoulder imbalance in such patients.

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity, affecting around 2% of adolescents worldwide. Genetic factors play an important role in its etiology. Using a genome-wide association study (GWAS), we recently identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To identify more AIS susceptibility loci relating to its severity and progression, we performed GWAS by limiting the case subjects to those with severe AIS. Through a two-stage association study using a total of ∼12,000 Japanese subjects, we identified a common variant, rs12946942 that showed a significant association with severe AIS in the recessive model (P=4.00 × 10(-8), odds ratio [OR]=2.05). Its association was replicated in a Chinese population (combined P=6.43 × 10(-12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new insight into the etiology and progression of AIS.

Background Although 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. Methods A 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. Results The GG genotype and G allele frequencies were significantly higher in the AIS patients than in the controls (χ 2 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). Conclusions This 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.

MESP2, HES7 and DUSP6 genes have been proved to be involved in the etiopathogenesis of congenital scoliosis (CS) in animal embryo studies, however, whether this association was detected in human CS patients also remains unknown. One hundred sporadic and non-syndromic CS patients and 100 age-matched normal controls were included in this study. Mutation screening of gene exons were performed by DNA sequencing. However, no mutation or new single nucleotide polymorphism was found in the exons of MESP2, HES7 and DUSP6 genes in CS patients and normal controls. MESP2, HES7 and DUSP6 genes may not be involved in the etiopathogenesis of sporadic and non-syndromic CS in Chinese Han population.

Study Design. A genetic association study to comprehensively investigate variations of neurotrophin 3 (NTF3) gene polymorphisms in a Chinese Han population. Objective. To explore whether the NTF3 gene polymorphisms are associated with the susceptibility, curve severity, or bracing effectiveness of adolescent idiopathic scoliosis (AIS). Summary of Background Data. 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. Methods. 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. Results. 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. Conclusion. 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.

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% p0.001) and the G allele (27.1 vs. 12.0%, p0.001) 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.

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 (P0.05), while this difference was not noted in group B (P0.05). 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 (P0.05). 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 (P0.05). 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 (P0.05). 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.

To investigate the association between the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene polymorphisms with the predisposition and disease severity of thoracic adolescent idiopathic scoliosis (AIS).Three hundred and fifty-four female thoracic AIS patients treated from January 2007 to March 2009 and 210 healthy female who underwent health examination during March 2005 to June 2006 as normal controls were recruited in this study. One SNP-418G/C (rs8179090) in the promoter region were selected for TIMP-2 gene. PCR- RFLP was used for genotyping.No significant differences of genotype and allele frequency distribution were found between AIS patients and normal controls (P0.05). In AIS patients, the frequency of C allele of the patients with the body mass index (BMI)17 kg/m(2) was significantly higher than those with the BMIor = 17 kg/m(2) (P0.05), and the frequency of C allele of cases with the major Cobb angleor = 40 degrees was significantly higher than that with Cobb angle40 degrees (P0.05). Among the patients who reached skeletal maturity without any interference of natural history, significantly higher average maximum Cobb angle was found in patients with GC and CC genotype compare with those with GG genotype.The SNP-418G/C (rs8179090) in the promoter region of TIMP-2 gene may be associated with abnormal growth pattern and curve progression of thoracic AIS. TIMP-2 gene is a disease-modifier gene of thoracic AIS.

Study design Case-control study. Objective This study is to replicate the association between the promoter polymorphisms of matrix metalloproteinase (MMP)-3 (-1171 5A/6A rs3025058) and interleukin (IL)-6 genes (-174G/C rs1800795) and adolescent idiopathic scoliosis (AIS) in a Chinese Han population. Summary of background data Recently, promoter polymorphisms in MMP-3 and IL-6 have been reported to be associated with AIS. Such genetic association, if confirmed by replication in other samples, would point to a primary degenerative defect in the disc or nucleus pulposus and inflammation as the key pathogenic mechanisms of AIS. Methods A total of 487 Chinese girls with AIS and 494 healthy age-matched adolescent girls were recruited consecutively during a 3-year period. The same genotyping technique as the original report was used to detect promoter polymorphisms of the MMP-3 and IL-6 genes. Statistical analysis of genotype frequencies between AIS patients and normal controls were performed by chi test. Results In this association study of the MMP-3 polymorphism and the risk of scoliosis, no significant difference was found between cases and controls, both in term of allelic association (6A: 81.2% in cases vs. 81.8% in controls, 5A: 18.8% in cases vs. 18.2% in controls, P = 0.745) or genotype association (6A/6A: 65.9% in cases vs. 66.2% in controls, 5A/6A: 30.6% in cases vs. 31.2% in controls, and 5A/5A: 3.5% in cases vs. 2.6% in controls; P = 0.733). Among AIS patients, the maximal Cobb angles were also not different among MMP-3 genotypes (6A/6A: 31.1 degrees +/- 9.7 degrees, 5A/6A: 29.1 degrees +/- 10.5 degrees, and 5A/5A: 29.4 degrees +/- 11.2 degrees; P = 0.392). As for IL-6 polymorphism, -174G/C polymorphism was not found in the Chinese AIS patients, and all 100 AIS patients and 100 normal controls were found to carry the G/G wild type. Conclusion This study did not find any significant association of promoter polymorphisms of the MMP-3 (-1171 5A/6A rs3025058) and IL-6 gene (-174G/C rs1800795) with AIS. The results indicate that the MMP-3 promoter polymorphism is not associated with AIS in the Chinese population. Further studies, however, are needed to rule out the potential association with other promoter polymorphisms in IL-6.

To investigate the melatonin signaling transduction pathway in BMSCs from adolescent idiopathic scoliosis patients.Twenty-four volunteers aged 12 - 18 years were divided into two groups: AIS group was 15 and control group was 9. The human bone marrow anticoagulated by heparin was obtained from anterior superior iliac spine, and the BMSCs were isolated by density gradient centrifuge from the mononuclear cells, and then were cultivated and serial subcultivated in vitro. P3 cultures were analyzed by the flow cytometry to determine the surface antigens. P3 BMSCs were used to detect the melatonin signaling transduction pathway. The cellular cAMP was elevated using forskolin, and then the BMSCs were treated with melatonin to inhibit the cellular cAMP levels.Mononuclear cells were cultivated and subcultivated to P3 culture in vitro, which were analyzed by the flow cytometry, and demonstrated that the expanded mononuclear cells expressed mesenchymal cell markers. The basal cAMP levels of the two groups were very low, after the stimulation of forskolin, cellular cAMP levels increased rapidly in all the patients, but after the stimulation of melatonin at physiological dose or even at pharmacological dose, there was no statistical difference of the inhibition of cAMP between AIS group and control (P0.05).Melatonin signaling transduction pathway may be normal in BMSCs from AIS patients.

To investigate the association of FBN3 gene polymorphism with abnormal growth pattern in adolescent idiopathic scoliosis (AIS) patients.Blood samples were obtained from 273 AIS patients, aged (14.6 +/- 2.1) (10 - 18), and 287 healthy age-matched females adolescents. The anthropometric parameters of the AIS group, including age, body height, weight, arm span, Cobb angle, time of menarche, and Risser's sign were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the FBN3 gene distribution.The genotype and allele frequency distribution were comparable between the AIS and normal control groups. There was no association with curve severity, arm span, BMI in patients with AIS. In the rs7257948, There were not significant differences in the FBN3 gene polymorphism sites rs35579498, rs12608849, and rs7257948, and allele distribution between these 2 groups. In the AIS group, the patients with GG genotype the number of those whose body height wasor = 160 cm was higher than those whose body height was160 cm (P = 0.01). In rs35579498, the frequency of allele T was relatively higher in the AIS patients than in the controls (P = 0.051). In the AIS patients, the expression rate of CT genotype in those whose menarche age wasor = 12 years was significantly higher than those whose menarche was12 years (P = 0.042).The polymorphisms of the 4 SNPs in the exons of FBN3 gene are neither associated with the occurrence nor the curve severity of AIS. However, in rs35579498, T allele appears to be overrepresented in the patients compared with the controls. Mutation in this site my plays a role in the occurrence and progression of AIS, and in rs7257948, polymorphism of FBN3 gene may be associated with body height of the AIS patients.

To investigate whether the growth hormone gene (GH) promotor polymorphism (rs2854184) is associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS).Two hundred and sixty-five AIS patients and 193 normal controls were recruited. The maximum Cobb angles were recorded in AIS patients. PCR-RFLP was used for the genotyping.The genotype frequency distribution were AA 38.3%, AT 50.3%, TT 11.4% in AIS patients and AA 39.6%, AT 50.2%, 10.1% TT in controls for the promotor polymorphism rs2854184 in GH gene. It was comparable between AIS and normal control. The allele frequency distribution was also comparable between AIS and normal control. It was 63.5% for allele A, 36.5% for allele T in AIS patients and 64.7% for allele A, 35.3% for allele T in normal control. The mean maximum Cobb angle in AIS patients with AA, AT, TT genotypes were 33.8 degrees +/- 10.0 degrees, 36.4 degrees +/- 15.0 degrees, 34.5 degrees +/- 9.1 degrees, respectively, it was similar with each other.The GH gene promoter polymorphism is neither associated with the occurrence nor the curve severity of AIS.

Background It has been recognised that genetic or hereditary factors may contribute to the aetiology of adolescent idiopathic scoliosis (AIS). Recently, two linkage analyses have identified 19p13.3 as the candidate region for AIS. The dipeptidyl peptidase 9 (DPP9) gene is located on chromosome 19p13.3. Objective To investigate whether DPP9 gene polymorphisms are associated with the occurrence or curve severity of AIS. Methods 571 girls with AIS and 236 normal controls were recruited. Using the Chinese data from the HapMap project, a set of tagging single-nucleotide polymorphisms (tagSNPs) were defined for the DPP9 gene. Five SNPs were genotyped by PCR restriction fragment length polymorphism. Statistical analysis of genotype frequencies between cases and controls was performed by the χ2 test. One-way analysis of variance was used to compare mean maximum Cobb angles with different genotypes in case-only analysis. Results Genotype frequencies were comparable between cases and controls for all five polymorphisms (p>0.05). The mean maximum Cobb angles of different genotypes were similar to each other for all five polymorphisms. Conclusions The DPP9 gene is not associated with the occurrence or curve severity of AIS. It is neither a disease-predisposition nor a disease-modifying gene of AIS.

To investigate body weight and the body mass index (BMI) in girls with adolescent idiopathic scoliosis (AIS).Six hundred and thirteen AIS female patients admitted from January 2005 to January 2007 and 449 healthy girls were recruited for this study with a range of age from 12 to 16 years old. The direct indexes included body height, body weight and date of birth. The indirect indexes included corrected body height, BMI and corrected BMI. The corrected body heights of AIS patients were adjusted by using the greatest Cobb angle to correct for spinal deformity according to Bjure's formula. Two-tailed Student's test was used for group comparison.In the AIS patients, the maximum Cobb angle was (31 +/- 11) degrees (11 degrees to 77 degrees). The corrected body height were significantly higher in AIS patients than in the normal controls from 12 to 16 years old (P0.05). The body weight were significantly lower in AIS girls than in normal controls from 12 to 16 years of age (P0.01). From 12 to 16 years of age, the BMI were (17.6 +/- 1.9), (17.9 +/- 2.5), (17.9 +/- 2.1), (18.6 +/- 2.3) and (19.0 +/- 1.9) kg/m2 in AIS patients; while the BMI were (19.5 +/- 3.4), (19.8 +/- 3.0), (20.4 +/- 2.9), (20.4 +/- 2.8) and (20.2 +/- 2.2) kg/m2 in normal controls. The BMI were significantly lower in AIS girls than the normal controls from 12 to 16 years of age (P0.001).After the onset of puberty, significantly longer corrected height, lower body weight and lower BMI were found in AIS patients. Results of this large-scale study revealed the presence of abnormal growth in AIS patients during peripubertal development.

STUDY DESIGN A genetic association study to investigate variation of the melatonin receptor 1A (MTNR1A) gene in adolescent idiopathic scoliosis (AIS) patients. OBJECTIVE To determine whether the MTNR1A gene promoter polymorphism is associated with the predisposition and/or disease severity of AIS. SUMMARY OF BACKGROUND DATA An involvement of the dysfunction of the melatonin pathway in the etiopathogenesis of AIS has been implicated in several studies. Recently, our group has found that the promoter polymorphism of the melatonin receptor 1B (MTNR1B) gene was associated with the occurrence of AIS. Hence, it is of interest to determine whether the promoter polymorphism of the MTNR1A gene could also associated with the occurrence or curve severity of AIS. METHODS A total of 226 AIS girls and 277 normal controls were recruited. SNP rs2119882 in the promoter region (-369 bp) of the MTNR1A gene was selected for the present study. Genotyping was performed by PCR-RFLP. Statistical analysis of genotype frequencies between case and control was performed by chi test. One-way ANOVA was used in comparison of mean maximum Cobb angles with different genotypes in case-only analysis. RESULTS Genotype and allele frequencies were comparable between case and control for SNP rs2119882 (P > 0.05). The mean maximum Cobb angles of different genotypes were similar with each other for SNP rs2119882. CONCLUSIONS Promoter polymorphism of the MTNR1A gene was not associated with the occurrence or curve severity of AIS. The MTNR1A gene may not be involved in the etiopathogenesis of AIS.

To investigate whether the MTNR1A gene promotor polymorphism (rs2119882) are associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS).226 AIS patients and 277 normal controls were recruited. The maximum Cobb angles were recorded in AIS patients. PCR-RFLP was used for the genotyping.The genotype and allele frequency distribution were comparable between AIS and normal control, the mean maximum Cobb angle of different genotypes of rs2119882 were similar with each other among AIS patients.The MTNR1A gene promoter polymorphism was neither associated with the occurrence nor the curve severity of AIS.

Study Design. A prospective study was designed to investigate the circulating leptin level in girls with adolescent idiopathic scoliosis (AIS). Objective. To determine the circulating leptin levels in AIS girls, and to investigate its associations with body mass and bone mass. Summary of Background Data. Abnormal growth pattern and osteopenia have been well documented in AIS patients throughout the peripubertal growth period. Leptin has been shown to regulate the growth of the whole body and bone particularly during childhood and adolescence. However, the circulating level of leptin, the relationships between leptin and lower body mass, and the relationships between leptin and lower bone mass in AIS patients remain unclear. Methods. One hundred twenty AIS girls and 80 healthy controls were recruited in this study. Measurements of anthropometry and circulating leptin were performed both in AIS and non-AIS girls. Evaluations of curve severity and measurements of bone mineral content/density (BMC/BMD) were performed only in AIS girls. The anthropometric data and circulating leptin levels were compared between older AIS girls and controls. The relationships between leptin and age, menstrual status, body weight, height, body mass index (BMI), Risser sign, curve magnitude, and BMC/BMD were analyzed in AIS girls. Results. Compared with healthy controls, an abnormal growth pattern (higher corrected height, lower weight, and lower BMI), and a marked decrease of circulating leptin were found in AIS girls, even after the adjustment for age and menstrual status. Positive correlations were found between leptin and age, menstrual status, body weight, height, BMI, and Risser sign. No significant correlation was found between leptin and curve magnitude. There was no significant difference in age at menarche between menstruating AIS and non-AIS girls, though an inverse correlation was observed between leptin and the age at menarche. The relationship between leptin and BMC/BMD remained significantly positive after controlling for age and menstrual status, although it was not independent of body weight or BMI. Conclusion. A marked decrease of circulating leptin was observed in the current study. There was an association between leptin and body weight, BMI, other growth parameters, and BMC/BMD. This correlation suggests that leptin might play an important role in the lower body and bone mass in AIS girls.

To investigate the association of vitamin D receptor (VDR) gene polymorphisms with abnormal growth pattern and low bone mass in adolescent idiopathic scoliosis (AIS) patients.Peripheral blood samples were obtained from 164 female patients with AIS, aged 14.4 +/- 2 (9 - 20), and 122 age-matched healthy girls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the VDR gene distributions.The frequency of Bb genotype was significantly higher in the AIS patients than in the controls (P0.01). The frequency of B alleles of the AIS patients was significantly higher than that of the controls (P0.01). In AIS patients, the expression rate of Aa genotype of the AIS patients with the body mass index (BMI)or = 18 kg/m(2) was significantly higher than those with the BMI18 kg/m(2) (P0.05), and the expression rate of Bb genotype of the AIS patients with the BMI18 kg/m(2) and arm span160 cm was significantly higher than that of the AIS patients with the BMIor = 18 kg/m(2) and arm spanor = 160 cm (P0.05).The BsmI site polymorphism of vitamin D receptor gene may be associated with abnormal growth pattern and low bone mass in girls with AIS.

Study Design. A genetic association study to comprehensively investigate variations of melatonin receptor 1B gene polymorphism by a set of tagging single nucleotide polymorphisms (tagSNPs) derived from the International Hapmap project. Objectives. To determine whether melatonin receptor 1B (MTNR1B) gene polymorphisms are associated with the predisposition and/or disease severity of adolescent idiopathic scoliosis (AIS). of Background Data. Linkage studies suggested a genetic predisposition for AIS. In addition, evidence showed that AIS might be related to melatonin deficiency and dysfunction of melatonin signaling pathway. Locating in one of the chromosomal regions linked to AIS, MTNR1B gene is a potential candidate gene for AIS. Methods. This study was carried out in 2-stage case-control analysis: 1) initial screening (472 cases and 304 controls) and 2) separate replication test (342 cases and 347 controls) to confirm results in the screening. In the first screening stage, 5 tagSNPs were selected to cover most of the genetic variation in the MTNR1B gene. In the second stage, SNPs showing association in the screening stage were studied in a separate replication sample set to confirm the association. Genotyping was performed by PCR-RFLP. Results. The first stage showed a putative association between rs4753426 and AIS, which was confirmed in the replication sample set. By meta-analysis, the frequency of C allele of this SNP locating in the promoter was significantly higher in the cases than controls (P = 0.006 after meta-analysis). Subjects with the CC genotype had an odds ratio of 1.29 for AIS. Another SNP rs741837 in promoter region, being moderate linkage disequilibrium with rs4753426, was also marginally associated with AIS. Conclusion. Polymorphisms of the promoter of MTNR1 B gene were associated with AIS, but not with the curve severity in AIS patients. This suggested that MTNR1 B was an AIS predisposition gene.

To investigate the correlation between the circulating leptin level and the anthropometric parameters and parameters related to pubertal growth, and to explore the role of leptin in the abnormal growth pattern in girls with adolescent idiopathic scoliosis (AIS).One hundred and twenty AIS girls selected randomly from the out-patient and in-patient departments, divided into 2 groups: Group A1 (n = 73, aged 10 - 13) and Group A2 (n = 47, aged 14 - 17), and 80 14 - 17 year-old healthy girl students receiving physical examination underwent measurement of body height and weight. Body mass index (BMI) was calculated. Peripheral fasting blood samples were collected to detect the level of leptin. The anthropometric data, pubertal status, and circulating leptin level were compared between the AIS girls and the controls. The relationships between leptin and age, menstrual status, body weight, height, BMI and Risser sign were analyzed in the AIS girls.Eighty-eight AIS girls (73%) and 14 healthy girls (18%) had a BMI score less than 18.0. The mean leptin level of Group A1 was 6.2 microg/L, significantly lower than of Group A2 (8.6 microg/L, P = 0.024). Compared with the healthy controls, the AIS girls had significantly greater corrected height (162.7 cm vs. 160.2 cm, P = 0.026), lower weight (44.3 kg vs. 53.6 kg, P = 0.01), lower BMI (17.5 kg/m(2) vs. 20.9 kg/m(2), P = 0.01), and lower circulating leptin (8.6 microg/L vs. 14.9 microg/L), even after the adjustment for age and menstrual status. An inverse correlation was observed between the leptin level and the age at menarche (AIS, r = -0.428, P0.001; controls, r = -0.280, P = 0.013). Whereas, positive correlations were found between leptin and age, menstrual status, body weight, height, BMI, and Risser sign (r = 0.234 - 0.506, P = 0.01 -0.001).AIS girls have markedly decreased circulating leptin level. Circulating leptin level is associated with body weight, BMI, and other growth parameters, suggesting that leptin may play an important role in the lower body mass in AIS girls.