Relationship between suppressor of cytokine signaling-3 gene polymorphism and growth pattern of adolescent idiopathic scoliosis
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ABSTRACT:
SUBMITTER: Qiao J
PROVIDER: S-EPMC4340211 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
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Project description:Most researchers agree that idiopathic scoliosis (IS) is a multifactorial disease influenced by complex genetic and environmental factors. The onset of the spinal deformity that determines the natural course of the disease, usually occurs in the juvenile or adolescent period. Transforming growth factors β (TGF-βs) and their receptors, TGFBRs, may be considered as candidate genes related to IS susceptibility and natural history. This study explores the transcriptional profile of TGF-βs, TGFBRs, and TGF-β responsive genes in the paravertebral muscles of patients with juvenile and adolescent idiopathic scoliosis (JIS and AIS, resp.). Muscle specimens were harvested intraoperatively and grouped according to the side of the curve and the age of scoliosis onset. The results of microarray and qRT-PCR analysis confirmed significantly higher transcript abundances of TGF-β2, TGF-β3, and TGFBR2 in samples from the curve concavity of AIS patients, suggesting a difference in TGF-β signaling in the pathogenesis of juvenile and adolescent curves. Analysis of TGF-β responsive genes in the transcriptomes of patients with AIS suggested overrepresentation of the genes localized in the extracellular region of curve concavity: LTBP3, LTBP4, ITGB4, and ITGB5. This finding suggests the extracellular region of paravertebral muscles as an interesting target for future molecular research into AIS pathogenesis.
| S-EPMC4181945 | biostudies-literature
Project description: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.
| S-EPMC3575984 | biostudies-literature
Project description:ObjectiveTo analyze the correlation between the polymorphism on interleukin 6 (IL-6) gene promoter region-174 locus and adolescent idiopathic scoliosis (AIS), including the susceptibility, the bracing effectiveness, and the possible mechanism.MethodsThe 182 AIS patients and 210 healthy controls who met the inclusion criteria between January 2013 and January 2016 were collected as research objects. The genotype of IL-6 gene promoter region-174 locus, the serum IL-6, the bone mineral density (BMD) of femoral neck and vertebrae (L 1-4), and the bone metabolism parameters, including bone alkaline phosphatase (BALP), bone gla protein (BGP), tartrate resistant acid phosphatase 5b (TRACP-5b), urine Ca, and urine Ca/Cr, were detected. All research objects were divided into the AIS group and the control group according to whether they had AIS, the GG, CG, CC groups according to their genotype, and progression-free group and progression group according to the therapeutic effectiveness of 1-year bracing treatment. Statistical analysis for the indexes were conducted respectively.ResultsThere were significant differences in AIS history, BMD of femoral neck and lumbar vertebrae between the AIS group and control group ( P<0.05). According to the therapeutic effecitveness of 1-year bracing treatment, 182 AIS patients were divided into progression-free group in 110 cases and progression group in 72 cases. The results of single factor analysis showed that there were significant differences in the genotype and allele distribution of IL-6 gene promoter region-174 locus, BMD of femoral neck and lumbar vertebrae, IL-6, TRACP-5b, urine Ca, and urine Ca/Cr between the progression-free group and progression group ( P<0.05). The results of multivariable analysis showed that the BMD of lumbar vertebrae, TRACP-5b, and urine Ca were the influencing factors of bracing efficacy ( P<0.05). According to the results of genotype detection, all research objects were divided into GG group in 264 cases, CG group in 104 cases, and CC group in 24 cases. The IL-6, TRACP-5b, urine Ca, and urine Ca/Cr of GG type carriers were higher and BMD of femoral neck and lumbar vertebrae were lower when compared with the CG and CC type carriers ( P<0.05). The BMD of lumbar vertebrae of CG type carriers was lower than that of CC type carriers ( P<0.05).ConclusionThe polymorphism of IL-6 genepromoter region-174 locus wasn't correlated with the AIS susceptibility, but it was correlated (not independently correlated) with the scoliosis progression under bracing treatment, and the risk for G-carried patients was higher. The mechanism may be that the polymorphism affected the IL-6 expression level and eventually affected the BMD of AIS patients through the bone metabolism.
| S-EPMC8414007 | biostudies-literature
Project description:BackgroundFibrillin-1 (FBN1) is an extracellular matrix glycoprotein essential to the structural component of microfibrils and FBN1 gene polymorphisms can be associated with adolescent idiopathic scoliosis (AIS) susceptibility. This study aimed to evaluate the potential role of the FBN1 rs12916536 polymorphism in AIS development or severity and the variation in Cobb angle in relation to patient's characteristics.MethodsDNA from 563 subjects (185 AIS patients and 378 controls) were genotyped using a validated TaqMan allelic discrimination assay. A multivariate logistic regression model evaluated the association between polymorphism and AIS, using the adjusted odds ratios (OR) with their respective 95% confidence intervals (95% CI). A linear regression analysis evaluated the variation in Cobb angle according to the patient's age and body mass index (BMI).ResultsAmong the AIS group there was a predominance of females (12:1), low or normal BMI (90%), 58% had a Cobb angle greater than 45° and 74% were skeletally mature. Age was a risk factor (4-fold) for curve progression higher than BMI (P < 0.001). The allelic frequency of the rs12916536 G > A polymorphism was 40% in controls and 31% in AIS cases; and this difference was statistically significant (P = 0.004). FBN1 rs12916536 GA + AA genotypes were associated with a lower risk of AIS susceptibility (OR = 0.58 and 95% CI = 0.35-0.98), after adjustment for age, sex and BMI. However, no significant differences were detected in polymorphism distribution with the severity of the disease (Cobb < 45° or ≥ 45°).ConclusionAge was a risk factor for progression of the scoliotic curve and FBN1 rs12916536 polymorphism a protective factor for AIS susceptibility.
| S-EPMC9077855 | biostudies-literature
Project description:Plasma exosomal miRNA may differ between adolescent idiopathic scoliosis patients and healthy individuals. Sequencing analysis was used to find these differential miRNAs.
2024-05-15 | GSE235203 | GEO
Project description:Adolescent Idiopathic Scoliosis (AIS) is the most common orthopedic condition requiring surgery, affecting 4% of adolescents. There is currently no proven method or prognostic test to identify symptomatic patients at risk of developing severe scoliosis who could benefit from growth-guided devices or minimally invasive non-fusion instrumentation surgeries. These innovative treatments must be performed at an early disease stage in younger patients to benefit from their growth potential. In this prospective cross-sectional study, we investigated the clinical utility of circulating microRNAs (miRNAs), an important class of small non-coding RNA, as biomarkers to predict the risk of developing severe scoliosis in AIS. Blood samples and clinical data were collected from 116 AIS patients who were followed until skeletal maturity and stratified according to their clinical outcome. Genome-wide expression profiling of miRNAs was performed with plasma obtained at the time of diagnosis of AIS (mean age of 13.3 ± 1.7 years with a mean Cobb angle of 24.4° ± 12.4°). This approach led to the identification of 15 circulating miRNAs that are upregulated in AIS patients who developed a severe scoliosis (Cobb angle ≥45°) at skeletal maturity compared to moderate and mild scoliosis groups (Cobb angle between 25°-44° and <25° respectively). After optimization and the application of Random Forest Models a panel of six miRNAs (miR-1-3p, miR-19a-3p, miR-19b-3p, miR-133b, miR-143-3p, and miR-148b-3p) out of 15 led us to develop an algorithm predicting the risk of developing a severe scoliosis with great accuracy (100%), sensitivity (100%) and specificity (100%). Having a scoliosis predictive bioassay and decision-making tools to predict curve progression in order to find the best treatment plan will undoubtedly transform the orthopedic care system in the field of pediatric scoliosis by integrating innovative precision medicine approaches. In addition, investigation of genes targeted by these miRNAs could fill our gaps in our understanding of AIS pathogenesis and reveal new actionable targets.
2025-01-12 | GSE286204 | GEO
Project description:Adolescent Idiopathic Scoliosis 1000 Exomes Study
| PRJNA488323 | ENA
Project description:Adolescent Idiopathic Scoliosis 1000 Exomes Study
| PRJNA488324 | ENA
Project description:Study designRetrospective Case-control Study.ObjectivesTo determine the requisite exercise compliance (EC) of physiotherapeutic scoliosis-specific exercise (PSSE) for achieving curve regression; to analyze whether the apical translation (AT), apical wedging (AW), and apical rotation (AR) of the major curve improve with regression effect.MethodsBetween 2019 and 2021, a total of 763 patients undertook a 6-month PSSE treatment. This resulted 426 compliable and 302 uncompliable patients remained available for analysis. For compliable patients, 213 with curve regression and 213 age-/sex-matched with curve stabilization/deterioration at the 6-month, were eligible for regression analysis to detect the relationship between EC and regression effect at the 6-month; receiver operating characteristic (ROC) curve analysis and Youden's index were applied to identify the threshold of EC leading to curve regression at the 6-month. The AT, AW, and AR of the major curve were compared before and after 6-month PSSE to investigate the radiographic parameters that improved with regression effect.ResultsEC was correlated with regression effect (odds ratio: 19.9, 95% confidence interval: 11.3-35.0, P < .001) and the cutoff threshold of EC was 4.4 h/week for 6 months to realize such an effect. AT was improved by 47.6% with curve regression, in which 152 cases remained curve regression and no case progressed into the operative threshold at the 1.5- to 2-year.ConclusionsA 6-month PSSE protocol of 4.4 hours per week was potentially leading to curve regression in treating mild to moderate scoliosis. An improvement in AT of the major curve was observed with the regression effect.
| S-EPMC10802514 | biostudies-literature
Project description:Generalized low bone mass and osteopenia have been reported in the axial and peripheral skeleton of adolescent idiopathic scoliosis (AIS) patients. Recently, many studies have shown that gene polymorphisms are related to osteoporosis. However, no studies have linked the association between gene polymorphisms and bone mass of AIS. Therefore, this study examined the association between the bone mass and RANKL, RANK, and OPG gene polymorphisms in 198 girls diagnosed with AIS. OPG 163 A --> G, 209 G --> A, 245 T --> G, and 1181 G --> C polymorphisms; RANK 421 C --> T and 575 C --> T polymorphisms; and RANKL rs12721445 and rs2277438 polymorphisms, as well as the bone mineral density at the lumbar spine (LSBMD) and femoral neck (FNBMD) were analyzed. The 163 A --> G, 209 G --> A, and 245 T --> G polymorphisms in the OPG gene were in complete linkage. No RANK 421 C --> T and 575 C --> T polymorphisms or RANKL rs12711445 polymorphism were observed. There was a significant association between the OPG gene 1181 G --> C polymorphism and LSBMD. LSBMD in AIS with the CC genotype was found to be significantly higher than in AIS with the GC (P < 0.05) or GG (P < 0.01) genotype. However, there was no significant association between LSBMD or FNBMD and the OPG gene 245 T --> G polymorphism or the RANKL rs2277438 polymorphism. These results suggest that the OPG gene 1181 G --> C polymorphism is associated with LSBMD in girls with AIS.
| S-EPMC2899432 | biostudies-literature