Transforming Growth Factor Beta 1 Is a Novel Susceptibility Gene for Adolescent Idiopathic Scoliosis

Ryzhkov, Igor I.; Борзилов, Е. Е.; Churnosov, Mikhail; Атаман, Олександр Васильович; Дедков, А. А.; Polonikov, Alexey

doi:10.1097/brs.0b013e31828de9e1

Cited by 37 publications

(39 citation statements)

References 23 publications

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“…Most of these associations have not been replicated in later larger studies [69–74]. Recent candidate gene studies have shown an association between IL - 17RC (interleukin 17 receptor C), TGFB1 (transforming growth factor beta 1), genes correlated with peak height velocity during puberty, DOT1L and C17orf67 , and IS [75–77]. …”

Section: Summary Of Genetic Findings In Idiopathic Scoliosismentioning

confidence: 99%

Genetics and pathogenesis of idiopathic scoliosis

2016

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Idiopathic scoliosis (IS), the most common spinal deformity, affects otherwise healthy children and adolescents during growth. The aetiology is still unknown, although genetic factors are believed to be important. The present review corroborates the understanding of IS as a complex disease with a polygenic background. Presumably IS can be due to a spectrum of genetic risk variants, ranging from very rare or even private to very common. The most promising candidate genes are highlighted.

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Section: Summary Of Genetic Findings In Idiopathic Scoliosismentioning

confidence: 99%

Genetics and pathogenesis of idiopathic scoliosis

2016

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“…However, the etiology of AIS is still unclear. Currently, AIS is thought to be multifactorial disorder; differing degrees of interaction between multiple factors depend on linear and summation causality [4,5]. Although AIS has been linked to multifactorial causes, genetic factors are considered the most important cause [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Association of GPR126 gene polymorphism with adolescent idiopathic scoliosis in Chinese populations

Yang

Pan

et al. 2015

Genomics

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Idiopathic scoliosis is the most common pediatric spinal deformity affecting 1% to 3% of the population, and adolescent idiopathic scoliosis (AIS) accounts for approximately 80% of these cases; however, the etiology and pathogenesis of AIS are still uncertain. The current study aims to identify the relationship between G protein-coupled receptor 126 (GPR126) gene and AIS predisposition, to identify the relationship between the genotypes of the GPR126 SNPs and the clinical phenotypes of AIS. We conducted a case-control study and genotyped twenty SNPs of GPR126 gene including ten exonic SNPs and ten intronic polymorphisms in 352 Chinese sporadic AIS patients and 149 healthy controls. We provided evidence for strong association of three intronic SNPs of the GPR126 gene with AIS susceptibility: rs6570507 A > G (p =0 .0035, OR = 1.729), rs7774095 A > C (p = 0.0078, OR = 1.687), and rs7755109 A > G (p = 0.0078, OR = 1.687). However, we did not identify any significant association between ten exonic SNPs of GPR126 and AIS. Linkage disequilibrium analysis indicated that rs7774095 A > C and rs7755109 A > G could be parsed into one block. The association between the intronic haplotype and AIS was further confirmed in an independent population with 110 AIS individuals and 130 healthy controls (p = 0.046, OR = 1.680). Furthermore, molecular mechanisms underlying intronic SNP regulation of GPR126 gene were studied. Although intronic SNPs associated with AIS didn't influence GPR126 mRNA alternative splicing, there was a strong association of rs7755109 A > G with decreased GPR126 mRNA level and protein levels. Our findings indicate that genetic variants of GPR126 gene are associated with AIS susceptibility in Chinese populations. The genetic association of GPR126 gene and AIS might provide valuable insights into the pathogenesis of adolescent idiopathic scoliosis.

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“…From animal models, LBX1 has been shown to play a critical role in muscular development. In addition, functional polymorphisms in the transforming growth factor beta (TGF-β) gene have been found to be associated with AIS susceptibility and in females to be associated with curve severity [53]. Abnormalities in TGF-β signalling are associated with several musculoskeletal disorders, including Duchenne muscular dystrophy [51], and it is a known inducer of muscle atrophy through induction in expression of muscle-specific ligase Atrogin-1 [19].…”

Section: Paraspinal Musclesmentioning

confidence: 99%

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Ede

Jones

2016

International Orthopaedics (SICOT)

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Adolescent idiopathic scoliosis (AIS) is now considered to be a multifactorial heterogeneous disease, with recent genomic studies supporting the role of intrinsic factors in contributing to the onset of disease pathology and curve progression. Understanding the key molecular signalling pathways by which these intrinsic factors mediate AIS pathology may facilitate the development of pharmacological therapeutics and the identification of predictive markers of progression. The heterogenic nature of AIS has implicated multiple tissue types in the disease pathophysiology, including spinal bone, intervertebral disc and paraspinal muscles. In this review, we highlight some of the mechanisms and intrinsic molecular regulators within these different tissue types and review the evidence for their involvement in AIS pathology.

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Transforming Growth Factor Beta 1 Is a Novel Susceptibility Gene for Adolescent Idiopathic Scoliosis

Abstract: This study, for the first time, highlights the importance of TGFB1 gene for the development and progress of AIS. We hypothesize several mechanisms by which the TGFB1 gene may contribute to spinal deformity in patients with AIS.

Cited by 37 publications

References 23 publications

Genetics and pathogenesis of idiopathic scoliosis

Genetics and pathogenesis of idiopathic scoliosis

Association of GPR126 gene polymorphism with adolescent idiopathic scoliosis in Chinese populations

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

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