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

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1191
Author(s):  
Patrick M. Carry ◽  
Elizabeth A. Terhune ◽  
George D. Trahan ◽  
Lauren A. Vanderlinden ◽  
Cambria I. Wethey ◽  
...  
Keyword(s):  
Idiopathic Scoliosis ◽  
Cobb Angle ◽  
False Discovery Rate ◽  
Energy Homeostasis ◽  
Monozygotic Twins ◽  
Differentially Methylated Region ◽  
Promoter Regions ◽  
False Discovery ◽  
Angle Difference ◽  
Curve Severity

Epigenetic mechanisms may contribute to idiopathic scoliosis (IS). We identified 8 monozygotic twin pairs with IS, 6 discordant (Cobb angle difference >10°) and 2 concordant (Cobb angle difference ≤2°). Genome-wide methylation in blood was measured with the Infinium HumanMethylation EPIC Beadchip. We tested for differences in methylation and methylation variability between discordant twins and tested the association between methylation and curve severity in all twins. Differentially methylated region (DMR) analyses identified gene promoter regions. Methylation at cg12959265 (chr. 7 DPY19L1) was less variable in cases (false discovery rate (FDR) = 0.0791). We identified four probes (false discovery rate, FDR < 0.10); cg02477677 (chr. 17, RARA gene), cg12922161 (chr. 2 LOC150622 gene), cg08826461 (chr. 2), and cg16382077 (chr. 7) associated with curve severity. We identified 57 DMRs where hyper- or hypo-methylation was consistent across the region and 28 DMRs with a consistent association with curve severity. Among DMRs, 21 were correlated with bone methylation. Prioritization of regions based on methylation concordance in bone identified promoter regions for WNT10A (WNT signaling), NPY (regulator of bone and energy homeostasis), and others predicted to be relevant for bone formation/remodeling. These regions may aid in understanding the complex interplay between genetics, environment, and IS.

scholarly journals CHD7 gene polymorphisms in female patients with idiopathic scoliosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Karolina Borysiak ◽  
Piotr Janusz ◽  
Mirosław Andrusiewicz ◽  
Małgorzata Chmielewska ◽  
Mateusz Kozinoga ◽  
...  
Keyword(s):  
Idiopathic Scoliosis ◽  
Cobb Angle ◽  
Gene Polymorphisms ◽  
Control Group ◽  
Polymorphism Analysis ◽  
Progression Rate ◽  
Study Group ◽  
Wild Allele ◽  
Genetic Examination ◽  
Curve Severity

Abstract Background The CHD7 (chromosome domain helicase DNA binding protein 7) gene has been associated with familial idiopathic scoliosis (IS) in families of European descent. The CHD7 single-nucleotide polymorphisms have never been studied in Polish Caucasian IS patients. Methods The aim of this study was to investigate the relationship of CHD7 gene polymorphisms with susceptibility to or progression of IS in Polish Caucasian females. The study group comprised 211 females who underwent clinical, radiological and genetic examination. The study group was analyzed in three subgroups according to: (1) Cobb angle (Cobb angle ≤30° vs. Cobb angle ≥35°), (2) age of diagnosis (adolescent IS vs. early-onset IS) and (3) rate of progression (non-progressive vs. slowly progressive vs. rapidly progressive IS). The control group comprised 83 females with no scoliosis and with a negative family history who underwent clinical and genetic examination. In total six CHD7 gene polymorphisms were examined. Three polymorphisms (rs1017861, rs13248429, and rs4738813) were examined by RFLP (restriction fragment length polymorphism) analysis, and three were quantified by Sanger sequencing (rs78874766, rs4738824, and rs74797613). Results In rs13248429, rs78874766, and rs74797613 polymorphisms only the wild allele was present. The rs1017861 polymorphism demonstrated an association with IS susceptibility (p < 0.01). Two polymorphisms, rs1017861 and rs4738813, were associated with curve severity and progression rate (p < 0.05). None of the evaluated polymorphisms in CHD7 gene showed any association with the age of IS onset. Conclusions The polymorphism rs1017861 in CHD7 gene showed an association with IS susceptibility. Two polymorphisms (rs1017861 and rs4738813) were associated with curve severity and progression rate. None of the evaluated polymorphisms in CHD7 gene showed any association with the age of IS onset. Further evaluation of CHD7 gene should be considered as IS modifying factor.

Upper instrumented vertebra to the right of the lowest instrumented vertebra as a predictor of an increase in the main thoracic curve after selective posterior fusion for the thoracolumbar/lumbar curve in Lenke type 5C adolescent idiopathic scoliosis: multicenter study on the relationship between fusion area and surgical outcome

2019 ◽  
Vol 31 (6) ◽  
pp. 857-864 ◽  
Author(s):  
Hiroki Oba ◽  
Jun Takahashi ◽  
Sho Kobayashi ◽  
Tetsuro Ohba ◽  
Shota Ikegami ◽  
...  
Keyword(s):  
Adolescent Idiopathic Scoliosis ◽  
Idiopathic Scoliosis ◽  
Cobb Angle ◽  
Posterior Fusion ◽  
Main Thoracic ◽  
Lowest Instrumented Vertebra ◽  
Line Tilt ◽  
The Right ◽  
Upper Instrumented Vertebra

OBJECTIVEUnfused main thoracic (MT) curvatures occasionally increase after selective thoracolumbar/lumbar (TL/L) fusion. This study sought to identify the predictors of an unacceptable increase in MT curve (UIMT) after selective posterior fusion (SPF) of the TL/L curve in patients with Lenke type 5C adolescent idiopathic scoliosis (AIS).METHODSForty-eight consecutive patients (44 females and 4 males, mean age 15.7 ± 2.5 years, range 13–24 years) with Lenke type 5C AIS who underwent SPF of the TL/L curve were analyzed. The novel “Shinshu line” (S-line) was defined as a line connecting the centers of the concave-side pedicles of the upper instrumented vertebra (UIV) and lowest instrumented vertebra (LIV) on preoperative radiographs. The authors established an S-line tilt to the right as S-line positive (S-line+, i.e., the UIV being to the right of the LIV) and compared S-line+ and S-line− groups for thoracic apical vertebral translation (T-AVT) and MT Cobb angle preoperatively, early postoperatively, and at final follow-up. The predictors for T-AVT > 20 mm at final follow-up were evaluated as well. T-AVT > 20 mm was defined as a UIMT.RESULTSAmong the 48 consecutively treated patients, 26 were S-line+ and 22 were S-line−. At preoperative, early postoperative, and final follow-up a minimum of 2 years later, the mean T-AVT was 12.8 mm (range −9.3 to 32.8 mm), 19.6 mm (range −13.0 to 41.0 mm), and 22.8 mm (range −1.9 to 68.7 mm) in the S-line+ group, and 10.8 mm (range −5.1 to 27.3 mm), 16.2 mm (range −11.7 to 42.1 mm), and 11.0 mm (range −6.3 to 26.9 mm) in the S-line− group, respectively. T-AVT in S-line+ patients was significantly larger than that in S-line− patients at the final follow-up. Multivariate analysis revealed S-line+ (odds ratio [OR] 23.8, p = 0.003) and preoperative MT Cobb angle (OR 7.9, p = 0.001) to be predictors of a UIMT.CONCLUSIONSS-line+ was defined as the UIV being to the right of the LIV. T-AVT in the S-line+ group was significantly larger than in the S-line− group at the final follow-up. S-line+ status and larger preoperative MT Cobb angle were independent predictors of a UIMT after SPF for the TL/L curve in patients with Lenke type 5C AIS. Surgeons should consider changing the UIV and/or LIV in patients exhibiting S-line+ during preoperative planning to avoid a possible increase in MT curve and revision surgery.

scholarly journals Sagittal profile modifications in hybrid versus all screw technique in adolescent idiopathic scoliosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Scaramuzzo ◽  
Antonino Zagra ◽  
Giuseppe Barone ◽  
Stefano Muzzi ◽  
Leone Minoia ◽  
...  
Keyword(s):  
Adolescent Idiopathic Scoliosis ◽  
Idiopathic Scoliosis ◽  
Cobb Angle ◽  
Thoracic Kyphosis ◽  
Sagittal Alignment ◽  
Vertical Axis ◽  
Sagittal Profile ◽  
Sacral Slope ◽  
Sagittal Vertical Axis ◽  
Lenke Classification

AbstractAim of the study was to evaluate sagittal parameters modifications, with particular interest in thoracic kyphosis, in patients affected by adolescent idiopathic scoliosis (AIS) comparing hybrid and all-screws technique. From June 2010 to September 2018, 145 patients were enrolled. Evaluation included: Lenke classification, Risser scale, coronal Cobb angle, thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS). Patients were divided in two groups (1 all-screws and 2 hybrid); a further division, in both groups, was done considering preoperative TK values. Descriptive and inferential statistical analysis was conducted. 99 patients were in group 1, 46 in group 2 (mean follow-up 3.7 years). Patients with a normo-kyphotic profile developed a little variation in TK (Δ pre–post = 2.4° versus − 2.0° respectively). Hyper-kyphotic subgroups had a tendency of restoring a good sagittal alignment. Hypo-kyphotic subgroups, patients treated with all-screw implants developed a higher increase in TK mean Cobb angle (Δ pre–post = 10°) than the hybrid subgroup (Δ pre–post = 5.4°) (p = 0.01). All-screws group showed better results in restoring sagittal alignment in all subgroups compared to hybrid groups, especially in hypo-TK subgroup, with the important advantage to give better correction on coronal plane.

Comparison of Changes in SRS-22 Values with Improvement in Cobb Angles after Posterior Fusion Surgery in Adolescent Idiopathic Scoliosis

2021 ◽  
Author(s):  
Kadir Gem ◽  
Sertan Hancioglu ◽  
Abdulkadir Bilgiç ◽  
Serkan Erkan
Keyword(s):  
Adolescent Idiopathic Scoliosis ◽  
Idiopathic Scoliosis ◽  
Cobb Angle ◽  
Posterior Instrumentation ◽  
Research Society ◽  
Posterior Fusion ◽  
Improvement Rate ◽  
Scoliosis Research Society ◽  
Correction Rate ◽  
Group B

Abstract Introduction The purpose of this study was to evaluate the relationship between the correction rate in Cobb angle and the improvement in quality of life profile in terms of Scoliosis Research Society (SRS)-22 values. Patients and Methods Between January 2007 and December 2013, posterior instrumentation and fusion was performed to 30 patients with adolescent idiopathic scoliosis (AIS). Patients were grouped according to their improvement rate in Cobb angles after surgery. Patients with an improvement rate of > 80% were grouped as Group A; those with an improvement rate of > 60% and ≤ 80% as Group B and those with an improvement rate of ≤ 60% were grouped as Group C. The SRS-22 questionnaire of these three groups was calculated and their relationship with the improvement in Cobb angle was evaluated. Results No statistical difference was found among the three groups in terms of pain, appearance, function, spirit, satisfaction, and SRS-22 values (all p > 0.05). Conclusion The results of this study demonstrate that the degree of correction rate does not correlate with the degree of improvement in the SRS-22 questionnaire in patients with AIS that underwent posterior fusion and instrumentation.

Predictive factors for correction rate in severe idiopathic scoliosis (Cobb angle ≥ 90°): an analysis of 128 patients

2021 ◽  
Author(s):  
Yuki Mihara ◽  
Weng Hong Chung ◽  
Siti Mariam Mohamad ◽  
Chee Kidd Chiu ◽  
Chris Yin Wei Chan ◽  
...  
Keyword(s):  
Idiopathic Scoliosis ◽  
Cobb Angle ◽  
Predictive Factors ◽  
Correction Rate

scholarly journals False Discovery Rate in Linkage and Association Genome Screens for Complex Disorders

Genetics ◽  
2003 ◽  
Vol 164 (2) ◽  
pp. 829-833
Author(s):  
Chiara Sabatti ◽  
Susan Service ◽  
Nelson Freimer
Keyword(s):  
Gene Mapping ◽  
False Discovery Rate ◽  
Disease Gene ◽  
Susceptibility Genes ◽  
Complex Disorders ◽  
Disease Gene Mapping ◽  
False Discovery ◽  
Simple Step ◽  
Multiple Comparison Procedure ◽  
Step Down

Abstract We explore the implications of the false discovery rate (FDR) controlling procedure in disease gene mapping. With the aid of simulations, we show how, under models commonly used, the simple step-down procedure introduced by Benjamini and Hochberg controls the FDR for the dependent tests on which linkage and association genome screens are based. This adaptive multiple comparison procedure may offer an important tool for mapping susceptibility genes for complex diseases.

Sign in / Sign up

Export Citation Format

Share Document