Dataset Information

Value of DNA methylation in predicting curve progression in patients with adolescent idiopathic scoliosis.

ABSTRACT: BACKGROUND:There is considerable discordance in the curve progression of adolescent idiopathic scoliosis (AIS) patients between monozygotic (MZ) twins, indicating that nongenetic factors must be involved in the curve progression of AIS patients. Epigenetic processes may constitute one of these factors and have not yet been investigated in relation to curve progression in AIS patients. METHODS:The genome and methylome of peripheral monocytes were compared between MZ twins discordant for curve progression. Sets of differentially methylated sites were validated using the MassARRAY platform of Sequenome on additional samples. RESULTS:In the discovery study, we found evidence suggesting a lack of differences at the genome sequence level and the presence of epigenetic differences related to the curve progression of AIS patients. The top 4 differentially methylated CpG sites associated with curve severity were tested, and only site cg01374129 (CpG site located at chr8:122583383, Hg19) was confirmed in two replication cohorts. The methylation levels of site cg01374129 were significantly lower in the progression group than in the nonprogression group. Cox regression analysis demonstrated that hypo-methylation of site cg01374129 was an independent prognostic factor for curve severity. Site cg01374129 methylation as a marker achieved a sensitivity of 76.4% and a specificity of 85.6% in differentiating between samples from patients with and without curve progression (AUC?=?0.827; 95% CI: 0.780 to 0.876). CONCLUSION:Increased curvature is associated with decreased methylation at site cg01374129. Our results indicate that methylation of site cg01374129 may therefore serve as a promising biomarker in differing between patients with and without curve progression.

SUBMITTER: Meng Y

PROVIDER: S-EPMC6197569 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Value of DNA methylation in predicting curve progression in patients with adolescent idiopathic scoliosis.

Meng Yichen Y Lin Tao T Liang Shulun S Gao Rui R Jiang Heng H Shao Wei W Yang Fu F Zhou Xuhui X Zhou Xuhui X

EBioMedicine 20180918

<h4>Background</h4>There is considerable discordance in the curve progression of adolescent idiopathic scoliosis (AIS) patients between monozygotic (MZ) twins, indicating that nongenetic factors must be involved in the curve progression of AIS patients. Epigenetic processes may constitute one of these factors and have not yet been investigated in relation to curve progression in AIS patients.<h4>Methods</h4>The genome and methylome of peripheral monocytes were compared between MZ twins discordan ...[more]

PMID: 30241917

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Project description:There is no consensus on the definition of a structural proximal thoracic curve (PTC) and the indications for fusion. As such, we assessed a single institute's experience in the management of large PTCs (>35 degrees) in patients with adolescent idiopathic scoliosis (AIS) who were either fused or not fused. A retrospective radiographic analyses of 30 consecutive AIS patients with double thoracic curves who underwent PSF with a minimum of 2 years' follow-up were included for review. The patients were divided into two groups: group 1 (n = 15 patients) with fusion extended up to T2 or T3 and group 2 (n = 15) with fusion limited to T5 or below. Shoulder balance was assessed according to clavicular angle, first-rib difference, and radiographic shoulder height difference (SHD). PTCs were defined based on a Cobb angle of >35, the presence of apical rotation, and a positive T1 tilt. The decision to fuse the PTC was based on curve magnitude only, with those between 35 and 45 degrees undergoing a selective fusion of the main thoracic curve (MTC), with both curves fused if the PTC was more than 45 degrees. In group 1, there were eight females and seven males. Their ages ranged between 12 and 33 years, with a mean of 16.2 ± 5.5 years. Postoperatively, the mean PTC correction was 45.6%, which statistically differed from preoperative status (p = 0.001). No statistical difference was noted in T1 tilt and the first-rib difference from preoperative to postoperative follow-up (p > 0.05). However, the clavicular angle and SHD were increased significantly at the immediate postoperative interval (p < 0.05) but demonstrated no significant changes between the initial and the last follow-up values (p > 0.05). Group 2 consisted of one male and 14 females. The mean age was 16.4 ± 4 years (range: 11 to 28 years). The mean spontaneous PTC correction was 28.3% and remained essentially unchanged at the end of the follow-up. The improvement in the curve from preoperative status was highly statistically significant (p = 0.001). All radiographic shoulder parameters exhibited a significant increase in the immediate postoperative period and at last follow-up, and shoulder balance improvement was not noted on follow-up. Although both groups were not statistically similar with regards to the preoperative PTC, AVR, apical vertebral translation, and shoulder parameters, no significant difference could be found in PTC or shoulder parameters between both groups at last follow-up (p > 0.05). Our study illustrates important observations that should be considered in defining the PTC for fusion consideration. Spontaneous correction of the PTC occurs in structural curves greater than 35 degrees and less than 45 degrees, and this correction is maintained over time. Despite that correction, radiographic shoulder parameters are expected to slightly increase. Nonfusion strategy may be appropriate for PTCs between 35 and 45 degrees. After fusion of both the MTC and the PTC, the radiographic shoulder parameters did not significantly differ. Preoperative radiographic shoulder parameters are not predictive of postoperative shoulder imbalance.

Project description:PURPOSE: 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. METHOD: 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 ? (ER?), estrogen receptor ? (ER?), 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 ?(2) test. A logistic regression analysis was used to figure out the independent predictors of the outcome of brace treatment. RESULTS: There were 90 cases (28.8%) in the failure group and 222 cases (71.2%) in the success group. Patients in the failure group were associated with the genotype GA (50.9 vs. 17.9% p < 0.001) and the G allele (27.1 vs. 12.0%, p < 0.001) at SNP rs9340799 of the ER? 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 ER? genes, we found no significant differences of the genotype or allele distribution between the two groups. In the logistic regression analysis, ER? and TPH-1 were demonstrated to be independent factors predictive of bracing effectiveness. CONCLUSIONS: ER? 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 ER? gene and the A allele at the rs10488682 site of the TPH-1 gene are prone to be resistant to brace treatment.

Project description:BackgroundAdolescent idiopathic scoliosis (AIS) which characterized by complex three-dimensional deformity of spine has been difficult to cure because of the unknown etiopathology and uncertainty of progression. Nowadays, circulating cell-free (ccf) DNA was found to be a potential biomarker for several benign and malignant diseases. However, whether ccf DNA can be a biomarker for AIS has not been reported yet. In this study, we investigate the circulating cell-free nuclear DNA (ccf n-DNA) and mitochondrial DNA (ccf mt-DNA) concentrations in the plasma of patients with AIS and controls (CT), and the changed plasma ccf n-DNA and ccf mt-DNA levels and their association with clinical parameters were assessed.MethodsThe plasma of peripheral blood from 69 AIS patients and 21 age-matched CT was collected for ccf DNA analysis. Quantitative PCR was used to detect ccf n-DNA and ccf mt-DNA levels, and correlation analyses between the ccf n-DNA and ccf mt-DNA levels and clinical characteristics were conducted. Receiver operator curves (ROC) were used to analyze the sensitivity and specificity of ccf n-DNA and ccf mt-DNA levels to different characteristics.ResultsThe plasma ccf n-DNA levels of both GAPDH and ACTB were significantly decreased in AIS patients compared with those in controls, while the plasma ccf mt-DNA levels did not changed. According to sex-related analyses, the ccf n-DNA levels in male CT-M was higher than that in female CT and male AIS, but the ccf n-DNA levels in female AIS was not significantly changed when compared with male AIS or female CT. However, the concentration of ccf mt-DNA in female AIS increased significantly when compared with male AIS. Surprisingly, Lenke type-related analyses suggested that Lenke type 1 patients had lower ccf n-DNA levels, whereas Lenke type 5 patients had higher ccf mt-DNA levels compared with those of controls. However, a lower sensitivity and specificity of AIS predicted by ccf n-DNA or ccf mt-DNA levels was observed, whether in total, by sex, or by Lenke type.ConclusionAlthough with no/little predictive accuracy of AIS/progressed AIS by ccf DNA levels, significantly changed plasma ccf DNA levels were observed in AIS patients compared with those in controls.

Dataset Information

Value of DNA methylation in predicting curve progression in patients with adolescent idiopathic scoliosis.

Publications

Value of DNA methylation in predicting curve progression in patients with adolescent idiopathic scoliosis.

Similar Datasets

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