An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis.
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ABSTRACT:
SUBMITTER: Ogura Y
PROVIDER: S-EPMC5856832 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis.
Ogura Yoji Y Takeda Kazuki K Kou Ikuyo I Khanshour Anas A Grauers Anna A Zhou Hang H Liu Gang G Fan Yan-Hui YH Zhou Taifeng T Wu Zhihong Z Takahashi Yohei Y Matsumoto Morio M Einarsdottir Elisabet E Kere Juha J Huang Dongsheng D Qiu Guixing G Xu Leilei L Qiu Yong Y Wise Carol A CA Song You-Qiang YQ Wu Nan N Su Peiqiang P Gerdhem Paul P Watanabe Kota K Ikegawa Shiro S
Scientific reports 20180316 1
Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 ...[more]
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Project description:Adolescent idiopathic scoliosis (AIS) is the most common type of spinal deformity and has a significant genetic background. Genome-wide association studies (GWASs) identified several susceptibility loci associated with AIS. Among them is a locus on chromosome 6q24.1 that we identified by a GWAS in a Japanese cohort. The locus is represented by rs6570507 located within GPR126. To ensure the association of rs6570507 with AIS, we conducted a meta-analysis using eight cohorts from East Asia, Northern Europe and USA. The analysis included a total of 6,873 cases and 38,916 controls and yielded significant association (combined P = 2.95 × 10-20; odds ratio = 1.22), providing convincing evidence of the worldwide association between rs6570507 and AIS susceptibility. In silico analyses strongly suggested that GPR126 is a susceptibility gene at this locus.
| S-EPMC6070519 | biostudies-literature
Project description:Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10(-13); odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS.
| S-EPMC4573260 | biostudies-literature
Project description:ObjectiveThe aim of this study was to compare serum vitamin D levels in girls with adolescent idiopathic scoliosis (AIS) and controls using meta-analysis methods. We searched Medline (via PubMed), Cochrane, Scopus, and Embase databases for studies evaluating outcomes in AIS, including patient age, body mass index, bone mineral density (BMD), and serum levels of parathyroid hormone (PTH), calcium, and phosphate, published between January 2000 and June 2020. We searched for studies that were limited to humans only. The inclusion criteria were a scoliosis study that measured vitamin D levels. We excluded duplicate publications such as review articles, case reports, and letters without original data. Two authors extracted data independently and resolved any discrepancies by consensus.ResultsEight comparative studies were identified. Demographic characteristics, bone density, serum levels of vitamin D, parathyroid hormone, and phosphate levels were not significantly different between AIS group and controls, except for serum calcium levels. The serum calcium levels were lower in AIS group than in the controls.ConclusionsThis review includes eight comparative studies reporting serum vitamin D and/or parathyroid hormone levels in AIS. Due to heterogeneity, a limited number of meta-analyses have shown a weak correlation between serum vitamin D levels and the incidence of AIS. Larger, multicenter studies are therefore needed to validate the results.
| S-EPMC10463820 | biostudies-literature
Project description:The Ladybird Homeobox 1 (LBX1) gene has been implicated in the etiology of adolescent idiopathic scoliosis (AIS). The association between LBX1 gene polymorphisms and AIS has been investigated in several studies. However, these findings have yield contradictory results rather than conclusive evidence.This study is to provide a meta-analysis of the published case-control studies on the association between LBX1 gene polymorphisms and AIS in Asian and Caucasian populations.This meta-analysis conformed to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We conducted a literature research on PubMed, Embase, Web of Science, and Cochrane Library until February 10, 2018. We included all case-control or cohort studies about association between LBX1 gene polymorphisms and AIS. The Risk Of Bias In Non-randomised Studies-of Interventions and Critical Appraisal Skills Programme were used to evaluate the risk of bias and study quality. We assessed the strength of association by pooled odds ratios (ORs) and 95% confidence intervals (CIs) in all genetic models under a fixed-effect model or random-effect model. We further performed subgroup analysis by ethnicity and sex. Sensitivity analysis and publication bias were also undertaken.A total of 10 studies (11,411 cases and 26,609 controls) were included in this meta-analysis. The pooled results showed a statistically significant association between LBX1 gene polymorphisms and AIS (for rs11190870, T vs C, OR = 1.54, 95% CI = 1.48-1.61, P < .00001; for rs625039, G vs A, OR = 1.50, 95% CI: 1.38-1.62; P < .00001; for rs678741, G vs A, OR = 0.74, 95% CI: 0.63-0.86; P < .0001; for rs11598564, G vs A, OR = 1.41, 95% CI: 1.31-1.51; P < .0001). For stratified analyses by ethnicity and sex, robust significant associations were detected in Asian and Caucasian populations, and in women and men under all genetic models.T allele of rs11190870 and G alleles of rs625039 and rs11598564 represent risk factors for AIS, but G allele of rs678741 may play a protective role in the occurrence of AIS. Further research is needed to confirm this finding and to understand its implications.
| S-EPMC6635165 | biostudies-literature
Project description:IntroductionThis study aimed to investigate the incidence of vitamin D deficiency in patients with adolescent idiopathic scoliosis through a meta-analysis and to analyze trends and risk factors.MethodsPotentially relevant studies were searched using the terms "Vitamin D AND scoliosis." Data on the incidence and risk factors, such as race, curve magnitude, and sex, were extracted from the selected studies. Review Manager 5.4 software was used for the data analysis. Six studies with a total of 1, 428 patients met the inclusion criteria.ResultsThe incidence of vitamin D insufficiency in patients with idiopathic scoliosis was 36.19% (95% CI [21.93 to 50.46]. In contrast, the incidence of vitamin D deficiency was 41.43% (95% CI [16.62 66.23]. Vitamin D levels were compared between Caucasian and African patients and it was concluded that Caucasian patients had a lower risk of vitamin D deficiency [RR 0.15, 95% CI (0.03 to 0.82; P = 0.03]. There was also an association between patients with idiopathic scoliosis and lower vitamin D -5.58, 95% CI [-7.10, -4.06]. Finally, no significant differences were observed in terms of curve magnitude assessed with the Cobb angle mean difference (MD) 4.45, 95% CI [-0.55, 9.44], or sex with lower-than-normal levels of vitamin D OR 0.96, 95% CI [0.58 to 1.60].DiscussionThe incidence rates of vitamin D insufficiency and deficiency in patients with adolescent idiopathic scoliosis were 36.19% and 41.43%, respectively. The Caucasian race was associated with a lower risk of vitamin D deficiency compared to the African race. Vitamin D deficiency was not related to curve magnitude or sex.
| S-EPMC10598863 | biostudies-literature
Project description:BackgroundRoutine screening of scoliosis is a controversial subject and screening efforts vary greatly around the world.MethodsConsensus was sought among an international group of experts (seven spine surgeons and one clinical epidemiologist) using a modified Delphi approach. The consensus achieved was based on careful analysis of a recent critical review of the literature on scoliosis screening, performed using a conceptual framework of analysis focusing on five main dimensions: technical, clinical, program, cost and treatment effectiveness.FindingsA consensus was obtained in all five dimensions of analysis, resulting in 10 statements and recommendations. In summary, there is scientific evidence to support the value of scoliosis screening with respect to technical efficacy, clinical, program and treatment effectiveness, but there insufficient evidence to make a statement with respect to cost effectiveness. Scoliosis screening should be aimed at identifying suspected cases of scoliosis that will be referred for diagnostic evaluation and confirmed, or ruled out, with a clinically significant scoliosis. The scoliometer is currently the best tool available for scoliosis screening and there is moderate evidence to recommend referral with values between 5 degrees and 7 degrees. There is moderate evidence that scoliosis screening allows for detection and referral of patients at an earlier stage of the clinical course, and there is low evidence suggesting that scoliosis patients detected by screening are less likely to need surgery than those who did not have screening. There is strong evidence to support treatment by bracing.InterpretationThis information statement by an expert panel supports scoliosis screening in 4 of the 5 domains studied, using a framework of analysis which includes all of the World Health Organisation criteria for a valid screening procedure.
| S-EPMC3835138 | biostudies-literature
Project description:BackgroundAdolescent idiopathic scoliosis is a common spinal deformity among children and adolescents worldwide with its etiology uncertain. Over a decade, a single nucleotide polymorphism rs10488682 in tryptophan hydroxylase 1 (TPH1) gene has been investigated in several association studies. We perform this study to summarize the current evidence of TPH1 rs10488682 polymorphisms and adolescent idiopathic scoliosis (AIS).MethodsSix databases were systematically searched: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Literature, and Wanfang database. Eligible case-control studies related to TPH1 and AIS were selected. Reference lists of them were reviewed for more available studies. Two authors independently screened and evaluated the literature and extracted data. The odds ratios and 95% confidence intervals were derived in association tests. Subgroup analysis was conducted by ethnicity. Sensitivity analysis was performed to examine the stability of the overall results.ResultsA total of 1006 cases and 1557 controls in 3 independent studies were included for meta-analysis. Statistical significance was discovered in heterozygote model (AT vs AA: OR = 1.741, 95%Cl = 1.100-2.753, P = .018 < .05, I2 = 0%), recessive model (AA vs AT + TT: OR = 0.640, 95%Cl = 0.414-0.990, P = .045 < .05, I2 = 0%) and over-dominant model (AT vs AA + TT: OR = 1.366, 95%Cl = 1.115-1.673, P = .003 < .05, I2 = 84.7%) in overall populations. Similar associations were also found in the Caucasian population. No significant associations were found in other genotypic comparisons and allelic comparisons.ConclusionsStatistically significant correlations were discovered between the TPH1 rs10488682 polymorphisms and AIS. Heterozygous AT genotype seems to be risky with an over-dominant effect. Ethnicity appears to modify the disease association.RegistrationNot applicable.
| S-EPMC7837909 | biostudies-literature
Project description:ObjectiveTo investigate whether: (i) rs12885713 (-16C > T) and rs5871 polymorphisms in the Calmodulin1 (CALM1) gene are predisposing factors for adolescent idiopathic scoliosis (AIS); and (ii) different single nucleotide polymorphisms (SNP) correlate with different subtypes of AIS.MethodsA total of 100 AIS patients with Cobb angle above 30° were recruited for this study together with 100 healthy controls. Curve pattern, Cobb angle, and Risser sign were recorded. Two polymorphic loci, rs12885713 (-16C > T) and rs5871 loci, of the CALM1 gene were analyzed. All patients were grouped according to the Peking Union Medical College (PUMC) classification, the apical location of the major curve, and the Cobb angle.ResultsThere was a statistically significant difference in the distribution of rs12885713 site polymorphism (P = 0.034) between PUMC type II (double curve) patients and controls, in the distribution of rs12885713 site polymorphism (P = 0.009) between lumbar curve cases and controls and in the distribution of rs5871 site polymorphism (P = 0.035) between thoracic curve patients and controls.ConclusionDifferent subtypes of AIS might be related to different SNP. The susceptibility of PUMC type II (double curve) AIS and lumbar curve might be related to CALM1 rs12885713 site polymorphism, while rs5871 site polymorphism might be a risk indicator for thoracic curve cases.
| S-EPMC6734643 | biostudies-literature
Project description:AimTo evaluate published data on the predictors of progressive adolescent idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of evidence.MethodsSelection criteria(1) study design: randomized controlled clinical trials, prospective cohort studies and case series, retrospective comparative and none comparative studies; (2) participants: adolescents with AIS aged from 10 to 20 years; and (3) treatment: observation, bracing, and other.Search methodOvid MEDLINE, Embase, the Cochrane Library, PubMed and patent data bases. All years through August 2014 were included. Data were collected that showed an association between the studied characteristics and the progression of AIS or the severity of the spine deformity. Odds ratio (OR), sensitivity, specificity, positive and negative predictive values were also collected. A meta-analysis was performed to evaluate the pooled OR and predictive values, if more than 1 study presented a result. The GRADE approach was applied to evaluate the level of evidence.ResultsThe review included 25 studies. All studies showed statistically significant or borderline association between severity or progression of AIS with the following characteristics: (1) An increase of the Cobb angle or axial rotation during brace treatment; (2) decrease of the rib-vertebral angle at the apical level of the convex side during brace treatment; (3) initial Cobb angle severity (> 25(o)); (4) osteopenia; (5) patient age < 13 years at diagnosis; (6) premenarche status; (7) skeletal immaturity; (8) thoracic deformity; (9) brain stem vestibular dysfunction; and (10) multiple indices combining radiographic, demographic, and physiologic characteristics. Single nucleotide polymorphisms of the following genes: (1) calmodulin 1; (2) estrogen receptor 1; (3) tryptophan hydroxylase 1; (3) insulin-like growth factor 1; (5) neurotrophin 3; (6) interleukin-17 receptor C; (7) melatonin receptor 1B, and (8) ScoliScore test. Other predictors included: (1) impairment of melatonin signaling in osteoblasts and peripheral blood mononuclear cells (PBMC); (2) G-protein signaling dysfunction in PBMC; and (3) the level of platelet calmodulin. However, predictive values of all these findings were limited, and the levels of evidence were low. The pooled result of brace treatment outcomes demonstrated that around 27% of patents with AIS experienced exacerbation of the spine deformity during or after brace treatment, and 15% required surgical correction. However, the level of evidence is also low due to the limitations of the included studies.ConclusionThis review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria.
| S-EPMC4539477 | biostudies-literature
Project description:BackgroundAdolescent idiopathic scoliosis (AIS) is the most common form of spinal deformity in children and adolescents which presents as complex three-dimensional (3D) deformity of the spine and rib cage. This study aimed to estimate the effectiveness and safety of surgical interventions for AIS using Bayesian meta-analysis.MethodsThe PubMed, EMBASE, and Cochrane Controlled Register of Trials were searched through Oct 1, 2019, without language restrictions. Relevant studies evaluating combined effectiveness and safety of surgical interventions for AIS were included according to eligibility criteria. The primary outcome measures included pulmonary function (change of absolute forced vital capacity and forced expiratory volume in 1 second from pre-operation to post-operation) and incidence of complications. The secondary outcome measure was change of Cobb angle from pre-operation to post-operation. Data was pooled using a random effects model in pairwise meta-analysis. Bayesian meta-analysis combined direct and indirect evidence using a Bayesian framework.ResultsTwenty-eight case-controlled studies with totally 1970 participants were included. This Bayesian meta-analysis combining direct and indirect evidences indicated that posterior fusion with instrumentation without thoracoplasty (PSF) had the highest probability to achieve better pulmonary function and lower complication rate; video assisted anterior fusion with instrumentation without thoracoplasty (VAT) had the highest probability to obtain better Cobb angle correction based on analysis of rank probability.ConclusionThis Bayesian meta-analysis demonstrated that PSF had the highest probability to achieve better post-surgical pulmonary function and lower complication rate, which gives a practical recommendation of PSF as a primary surgical treatment for AIS. The results also support statistics that current surgeries adopted more PSF but less open anterior approach surgery and thoracoplasty. More research work is required to address the effectiveness and safety of VAT for treating AIS more convincingly.
| S-EPMC7333422 | biostudies-literature