Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis

Abstract

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 a (ERa), estrogen receptor b (ERb), 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 v 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 ERa 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 ERb genes, we found no significant differences of the genotype or allele distribution between the two groups. In the logistic regression analysis, ERa and TPH-1 were demonstrated to be independent factors predictive of bracing effectiveness. Conclusions ERa 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 ERa gene and the A allele at the rs10488682 site of the TPH-1 gene are prone to be resistant to brace treatment.

XbaI and PvuII Polymorphisms of Estrogen Receptor 1 Gene in Females with Idiopathic Scoliosis: No Association with Occurrence or Clinical Form

“…However, Tang et al demonstrated no association of XbaI polymorphism, either with occurrence, or with Cobb angle, nor with anthropometric measurements in the Chinese Han population [16]. In 2011, Xu et al performed a study in the Chinese population and suggested that the X (G) allele at the rs9340799 might be a potential genetic marker, predicting the outcome of brace treatment for IS [17].…”

Association between the ESR1 -351A>G single nucleotide polymorphism (rs9340799) and adolescent idiopathic scoliosis: a systematic review and meta-analysis

“…One study in an independent Japanese population found a marginally significant association between rs9340799 and curve severity represented by the mean Cobb angle (p = 0.0509) [10], while two other studies in Chinese [9] and Polish Caucasian [11] populations found no association. There is also limited evidence that rs9340799 may play a role in the effectiveness of brace treatment, where patients with the G allele were significantly more likely to be resistant to brace treatment [26], and in the risk for operative treatment and curve progression [7]. These clinical correlations have potential applications in personalized medicine; genetic information can be incorporated into risk prediction models for the prevention [27] and treatment of AIS, such as genetic testing for the risk of severe spinal curve progression [28].…”

Does brace treatment impact upon the flexibility and the correctability of idiopathic scoliosis in adolescents?

“…Currently, the standard of care for AIS patients includes the following options: observation, for patients with a small curve or skeletal maturity; brace treatment, for those with a mild or moderate curve and skeletal immaturity; and surgical correction, for those with a severe curve [2]. Until now, brace treatment has served as a vital non-surgical procedure for immature AIS patients with a mild or moderate curve, because bracing can effectively halt curve progression and prevent surgical intervention in some cases [17,19,23,31,34,35]. To date, several types of brace devices have been developed, such as the Milwaukee [17], Boston [19], Charleston [25], Providence [32], Rosenberger [24], Wilmington [1] and Chêneau [34].…”