Curve Severity In Adolescent Idiopathic Scoliosis Research Articles

Hounsfield unit for assessing asymmetrical loss of vertebral bone mineral density and its correlation with curve severity in adolescent idiopathic scoliosis.

BackgroundLow bone mass concomitantly occurs in patients with adolescent idiopathic scoliosis (AIS) and can persist until skeletal maturity. The purpose of this study was to assess the asymmetrical loss of vertebral bone mineral density (vBMD) and its correlation with curve severity in patients with AIS using Hounsfield unit (HU) values measured from computed tomography scans.MethodsA total of 93 AIS patients were retrospectively recruited. The HU values of the vertebral body (VB-HU) and pedicle screw trajectory (PST-HU) were measured from four vertebrae above (Apex − 4) to four below (Apex + 4) the apical vertebra (Apex) of the major curve. The VB-HU and PST-HU at the upper end vertebra, Apex, and lower end vertebra within the concave and convex sides of the major and minor curves and stable vertebrae were obtained.ResultsA significant correlation was found between the Cobb angle and VB-HU at the periapical levels of the major curve. VB-HU and PST-HU at periapical levels were significantly greater within the concavity than the convexity of both major and minor curves. The asymmetric ratios of VB-HU and PST-HU were significantly correlated with the major curve Cobb angle, peaked at the apex, and gradually diminished from the apex to the end vertebrae. The asymmetrical loss of vBMD aggravated with the progression of curve severity, presenting as VB-HU, significantly decreased within the convexity and insignificantly decreased within the concavity of the major curve.ConclusionThe asymmetrical loss of vBMD was associated with the progression of curve severity in AIS. For patients with severe AIS, the distraction of the pedicle screws at the concave side should be a priority in correcting the major curve, and supplemental anchors and larger-sized screws should be placed within the convex side around the apex of the major curve to reduce the risk of screw loosening after surgery.

Genetic variant of MIR4300HG is associated with progression of adolescent idiopathic scoliosis in a Chinese population

BackgroundA recent genome-wide association study identified a susceptible locus in MIR4300HG gene that was associated with curve progression of adolescent idiopathic scoliosis (AIS) in the Japanese population. However, the association between the gene and curve progression in other populations remains unclear.MethodsA cohort of 1952 AIS patients and 2495 healthy controls were included in the case-control analysis. In the case-only analysis, 747 patients were assigned to the progression group and 520 patients were assigned to the non-progression group, respectively. Rs35333564 was genotyped for all the subjects. Paraspinal muscles of 76 patients were collected for the analysis of gene expression. Chi-square test and ANOVA test were used for the intergroup comparison. Pearson correlation analysis was performed to investigate the relationship between the gene expression and curve magnitude.ResultsVariant rs35333564 was significantly associated with the curve severity of AIS (p = 0.025), but not the development of AIS (p = 0.418). Genotype GG was indicated by remarkably lower expression of MIR4300 (p = 0.020) which was significantly correlated with curve magnitude (p = 0.010). As a predicted target gene of MIR4300, the expression of CRTC1 was negatively correlated with MIR4300 expression (p = 0.012, r = −0.287) and positively correlated with curve severity (p = 0.025, r = 0.257).ConclusionsThe association between rs35333564 and curve progression was successfully replicated in a Chinese AIS population. CRTC1 may be the target gene of MIR4300 that plays a role in the curve progression of AIS.

New Evidence Supporting the Role of FBN1 in the Development of Adolescent Idiopathic Scoliosis.

A genetic association study. To determine whether common variants of fibrillin-1 (FBN1) and fibrillin-2 (FBN2) are associated with adolescent idiopathic scoliosis (AIS), and to further investigate to further investigate the functional role of FBN1 in the onset and progression of AIS. Previous studies have identified several rare variants in FBN1 and FBN2 that were associated with AIS. There is, however, a lack of knowledge concerning the association between common variants of FBN1 and FBN2 and AIS. Common variants covering FBN1 and FBN2 were genotyped in 952 patients with AIS and 1499 controls. Paraspinal muscles were collected from 66 patients with AIS and 18 patients with lumbar disc herniation (LDH) during surgical interventions. The differences of genotype and allele distributions between patients and controls were calculated using Chi-square test. The Student t test was used to compare the expression of FBN1 and FBN2 between patients with AIS and LDH. One-way analysis of variance test was used to compare the gene expression among different genotypes of the significantly associated variant. The Pearson correlation analysis was used to determine the relationship between FBN1 expression and the curve severity. The common variant rs12916536 of FBN1 was significantly associated with AIS. Patients were found to have significantly lower frequency of allele A than the controls (0.397 vs. 0.450, P = 1.10 × 10) with an odds ratio of 0.81. Moreover, patients with AIS were found to have significantly lower FBN1 expression than patients with LDH (0.00033 ± 0.00015 vs. 0.00054 ± 0.00031, P = 1.70 × 10). The expression level of FBN1 was remarkably correlated with the curve severity (r = -0.352, P = 0.02). There was no significant difference of FBN1 expression among different genotypes of rs12916536. Common variant of FBN1 is significantly associated with the susceptibility of AIS. Moreover, the decreased expression of FBN1 is significantly correlated with the curve severity of AIS. The functional role of FBN in AIS is worthy of further investigation. 3.

Correlation Between Hump Dimensions and Curve Severity in Idiopathic Scoliosis Before and After Conservative Treatment

Prospective study in 150 consecutive outpatients affected by adolescent idiopathic scoliosis (AIS). The purposes were to (1) identify a correlation between hump dimensions and the severity of scoliotic curve, and (2) evaluate how the treatment influenced the main parameters of scoliosis. The existence of a relationship between clinical deformities and curve severity in AIS is still debated. Furthemore, only a few studies have investigated the effectiveness of conservative treatment for idiopathic scoliosis taking into account both clinical and radiologic factors. 150 consecutive outpatients (mean age 12.8 ± 1.9 years) affected by AIS were subjected to conservative brace-based treatment. 134 participants completed the treatment protocol. Two parameters were considered to evaluate the treatment progress: the hump and the Cobb angle. Measurements were determined at the beginning and the end of treatment. Statistical analyses were performed in the whole sample and after dividing the study participants into 4 subgroups: patients with lumbar (n = 66) or thoracic curves (n = 68), patients ranging in age between 6 and 13 years (n = 89) and patients ≥ 14 years of age (n = 45). A positive correlation was detected between the hump dimension and curve severity at the beginning and the end of treatment, except for lumbar curves at baseline. The deformity was effectively corrected by the orthotic treatment (Cobb angle: 29.4 ± 8.5° at baseline and 19.3 ± 9.8° at the end of treatment; hump severity: 11.6 ± 5.6 mm at baseline and 6.2 ± 4.6 mm at the end). In addition, our data indicate that the hump correction is more evident than that of the curve registered in Cobb degrees. A significant correlation exists between the hump dimension and curve severity both at the beginning and the end of treatment, except for lumbar curves at baseline. The brace treatment confirmed its effectiveness in arresting the deformity progression and inducing a remodeling both of the scoliotic curve and the hump.

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.

Analysis of Single Nucleotide Polymorphism in Adolescent Idiopathic Scoliosis in Korea: For Personalized Treatment

PurposeThe incidence of adolescent idiopathic scoliosis (AIS) has rapidly increased, and with it, physician consultations and expenditures (about one and a half times) in the last 5 years. Recent etiological studies reveal that AIS is a complex genetic disorder that results from the interaction of multiple gene loci and the environment. For personalized treatment of AIS, a tool that can accurately measure the progression of Cobb's angle would be of great use. Gene analysis utilizing single nucleotide polymorphism (SNP) has been developed as a diagnostic tool for use in Caucasians but not Koreans. Therefore, we attempted to reveal AIS-related genes and their relevance in Koreans, exploring the potential use of gene analysis as a diagnostic tool for personalized treatment of AIS therein.Materials and MethodsA total of 68 Korean AIS and 35 age- and sex-matched, healthy adolescents were enrolled in this study and were examined for 10 candidate scoliosis gene SNPs.ResultsThis study revealed that the SNPs of rs2449539 in lysosomal-associated transmembrane protein 4 beta (LAPTM4B) and rs5742612 in upstream and insulin-like growth factor 1 (IGF1) were associated with both susceptibility to and curve severity in AIS. The results suggested that both LAPTM4B and IGF1 genes were important in AIS predisposition and progression.ConclusionThus, on the basis of this study, if more SNPs or candidate genes are studied in a larger population in Korea, personalized treatment of Korean AIS patients might become a possibility.

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.

Abnormal Leptin Bioavailability in Adolescent Idiopathic Scoliosis

This was a cross-sectional study. The present study aimed to explore the differences in leptin bioavailability between adolescent idiopathic scoliosis (AIS) and healthy age-matched girls in a Chinese Han population. AIS is a common spinal deformity mainly occurring in girls during the peripubertal period. The development of scoliosis is related to relative anterior spinal overgrowth. AIS girls also have associated lower body mass index (BMI) and lower bone mineral status. Leptin, together with soluble leptin receptor (sOB-R), was shown to play an important role in the regulation of bone and energy metabolism in children. It was hypothesized that leptin and sOB-R are abnormal and associated with deranged growth and anthropometric phenotypes in AIS girls. Serum leptin and sOB-R were measured together with documentation of anthropometric parameters and clinical data in 95 AIS girls and 46 healthy matched controls (age 11-16 years). Serum leptin and sOB-R concentrations were measured by enzyme-linked immunosorbent assay and correlated with the different measured parameters. AIS girls had significantly lower BMI and longer arm span than healthy controls. AIS girls were found to have significantly higher sOB-R levels and lower free leptin index (FLI) after adjusting for age and body weight in multivariate regression analysis. Significant correlation was found between sOB-R, FLI, and curve severity in AIS girls. This is the first study demonstrating the presence of abnormal leptin bioavailability in AIS girls that might play an important role in the etiopathogenesis of AIS. Further investigation is required to provide a better understanding of the underlying mechanisms, with the aim to explore the potential clinical application as a biomarker for predicting curve initiation or progression in AIS.

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.

Association between tartrate-resistant acid phosphatase 5 gene polymorphism and adolescent idiopathic scoliosis

To investigate whether the titrate-resistant acid phosphatase 5 (ACP5) gene polymorphisms were associated with the occurrence or curve severity of adolescent idiopathic scoliosis (AIS). There were 372 AIS patients from January 2006 to December 2008 and 239 normal controls from March 2005 to August 2006 were recruited. The Cobb angles were ≥ 10° in all AIS patients. Using the haplotype data of Han population from the Hapmap Project, two tag SNPs (rs2229531, rs2071484) were defined for ACP5 gene. PCR-restriction fragment length polymorphism was used for the genotyping. No polymorphism in rs2229531 was found in this study. The genotype and allele frequency distribution in rs2071484 were similar between AIS patients and normal controls (χ(2) = 3.336 and 1.438, P > 0.05). The mean maximum Cobb angles of different genotypes of rs2071484 in ACP5 gene were 38° ± 19° in AA, 34° ± 14° in AG and 38° ± 21° in GG, which were similar with each other among AIS patients who reached skeletal maturity or received surgery treatment (P = 0.157). The ACP5 gene is neither associated with the occurrence nor the curve severity of AIS.

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.

Genetic polymorphism of growth hormone gene in adolescent idiopathic scoliosis

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.

Association study between adolescent idiopathic scoliosis and the DPP9 gene which is located in the candidate region identified by linkage analysis

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...

Lack of Association Between the Promoter Polymorphism of the MTNR1A Gene and Adolescent Idiopathic Scoliosis

A genetic association study to investigate variation of the melatonin receptor 1A (MTNR1A) gene in adolescent idiopathic scoliosis (AIS) patients. To determine whether the MTNR1A gene promoter polymorphism is associated with the predisposition and/or disease severity of AIS. 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. 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. 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. 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.

Effect of genetic polymorphism of MTNR1A gene on adolescent idiopathic scoliosis

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.