Methylation of Estrogen Receptor 1 Gene in the Paraspinal Muscles of Girls with Idiopathic Scoliosis and Its Association with Disease Severity

Abstract

Idiopathic scoliosis (IS) is a multifactorial disease with epigenetic modifications. Tissue dependent and differentially methylated regions (T-DMRs) may regulate tissue-specific expression of the estrogen receptor 1 gene (ESR1). This study aimed to analyze methylation levels within T-DMR1 and T-DMR2 and its concatenation with ESR1 expression of IS patients. The study involved 87 tissue samples (deep paravertebral muscles, both on the convex and the concave side of the curve, and from back superficial muscles) from 29 girls who underwent an operation due to IS. Patient subgroups were analyzed according to Cobb angle ≤70° vs. >70°. Methylation was significantly higher in the superficial muscles than in deep paravertebral muscles in half of the T-DMR1 CpGs and all T-DMR2 CpGs. The methylation level correlated with ESR1 expression level on the concave, but not convex, side of the curvature in a majority of the T-DMR2 CpGs. The T-DMR2 methylation level in the deep paravertebral muscles on the curvature’s concave side was significantly lower in patients with a Cobb angle ≤70° in four CpGs. DNA methylation of the T-DMRs is specific to muscle tissue location and may be related to ESR1 expression regulation. Additionally, the difference in T-DMR2 methylation may be associated with IS severity.

Epigenetic and Genetic Factors Related to Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Scoping Review of the Current Literature

“…According to the research performed, a total of 40 papers [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ] met the inclusion criteria and were considered for review. Of these studies, twenty-one [ 18 , 19 , 21 , 24 , 31 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 44 , 45 ,…”

“…According to the Oxford level of evidence scale, ten [ 16 , 17 , 27 , 28 , 29 , 32 , 46 , 48 , 49 , 53 ] of the included studies had a level of evidence IV, twenty-six [ 18 , 19 , 20 , 21 , 23 , 24 , 26 , 31 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 44 , 45 , 47 , 50 , 51 , 52 , 54 , 55 ] studies had a level of evidence III, while the remaining studies had a level of evidence II [ 22 , 25 , 30 , 43 ].…”

“…The median age at the first visit ranged from 12.2 ± 1.2 to 18.5 ± 1.8 years and the median follow-up ranged from 12 months to 42 months. Asiatic populations (Chinese, Japanese, and Korean) [ 9 , 16 , 17 , 20 , 21 , 23 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 42 , 43 , 44 , 45 , 47 , 51 , 53 , 54 , 55 , 56 ] were the most studied by authors, but Caucasian populations (Europeans, Polish, and French-Canadian) [ 24 , 25 , 26 , 27 , 41 , 43 , 46 , 48 , 49 , 52 ], Russian [ 19 ], and Turkish [ 18 ] populations were also evaluated for possible associations. Two studies did not accurately describe the population demographics [ 30 , 43 ].…”

Severity of Idiopathic Scoliosis Is Associated with Differential Methylation: An Epigenome-Wide Association Study of Monozygotic Twins with Idiopathic Scoliosis

“…Targeted studies have reported associations between methylation and IS near the COMP [73] and PITX1 [74] genes. Two recent studies [75,76] of ESR1 and ESR2 methylation from paravertebral muscle tissue in females with IS supports potential interrelationship between sex hormone levels, methylation, and the clinical manifestation of IS. ESR1 methylation levels from paravertebral muscle tissue on the concave side of curve were associated with curve severity [75], and furthermore, ESR2 promoter methylation levels differed between concave and convex sides of the curves [76].…”

“…Two recent studies [75,76] of ESR1 and ESR2 methylation from paravertebral muscle tissue in females with IS supports potential interrelationship between sex hormone levels, methylation, and the clinical manifestation of IS. ESR1 methylation levels from paravertebral muscle tissue on the concave side of curve were associated with curve severity [75], and furthermore, ESR2 promoter methylation levels differed between concave and convex sides of the curves [76]. Epigenome-wide discovery analyses in MZ twins are limited to studies including only one [77] and two [78] MZ twin pairs discordant for IS.…”