Value of DNA Methylation in Predicting Curve Progression in Patients with Adolescent Idiopathic Scoliosis

Abstract

Background: There is considerable discordance for adolescent idiopathic scoliosis (AIS) patients' curve progression between monozygotic (MZ) twins, indicating that non-genetic factors must be involved in 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 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 both two replication cohorts. Methylation levels of site cg01374129 were significantly lower in progression group compared with non-progression group. Cox regression analysis demonstrated hypo-methylation of site cg01374129 as 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 curve 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. Funding: This research was supported by grants from Translational Medicine Centre of Second Military Medical University for Precision Medicine (2017JZ25) and the National Natural Science Foundation of China (81772305) to XZ. Declaration of Interest: None declared. Ethical Approval: The ethical committee and institutional review board of Shanghai Changzheng Hospital approved this study.