Alexandros G .Sfakianakis,ENT,Anapafeos 5 Agios Nikolaos Crete 72100 Greece,00302841026182

Τρίτη 26 Σεπτεμβρίου 2017

Quantitative evaluation of the relationship between COMP promoter methylation and the susceptibility and curve progression of adolescent idiopathic scoliosis

Abstract

Purpose

The cartilage oligomeric matrix protein (COMP) was reported to be down-regulated in adolescent idiopathic scoliosis (AIS). The purposes of the study were to evaluate the roles of COMP promoter methylation on the abnormal gene expression and the epigenetic phenotype in AIS.

Methods

DNA samples of 50 AIS patients and 50 healthy controls were analyzed. Five CpG sites of COMP gene were amplified and sequenced using the polymerase chain reaction (PCR) and the pyrophosphate sequencing technology, while the COMP gene expression was evaluated using real-time PCR. Comparisons were analyzed with the Chi-square test and independent t test. Pearson coefficients of correlation were used to evaluate the association between gene methylation and clinical phenotypes.

Results

The average COMP gene promoter methylation of the AIS and control groups was 12.26 ± 2.36 and 8.76 ± 1.94 (p < 0.0001), and correspondingly the relative expression of COMP gene expression was 0.52 ± 0.12 and 1.16 ± 0.52 (p < 0.001), respectively. The correlation analysis showed significantly negative correlation between methylation level and gene expression (p < 0.0001). The comparison analysis between AIS patients with positive and negative methylation showed significant difference in chronological age (p < 0.001) and Cobb angle of main curve (p = 0.011). The methylation level of the COMP promoters was significantly correlated with Cobb angle of main curve and age (p < 0.0001) among the five CpG sites.

Conclusions

AIS patients had significantly high COMP promoter methylation and low gene expression. Positive and high COMP promoter methylation was correlated with young age and high Cobb angle of main curve. Therefore, COMP gene promoter methylation may provide significant prognostic information in predicting the susceptibility and curve progression of AIS.



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