The Susceptibility and Potential Functions of the LBX1 Gene in Adolescent Idiopathic Scoliosis.

Yueming Song,Shishu Huang,Ming Luo,Yuxiao Zhang

doi:10.3389/fgene.2020.614984

Yueming Song, Shishu Huang + Show 2 more

Open Access

https://doi.org/10.3389/fgene.2020.614984

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Abstract

Genome-wide association studies have identified many susceptibility genes for adolescent idiopathic scoliosis (AIS). However, most of the results are hard to be replicated in multi-ethnic populations. LBX1 is the most promising candidate gene in the etiology of AIS. We aimed to appraise the literature for the association of LBX1 gene polymorphisms with susceptibility and curve progression in AIS. We also reviewed the function of the LBX1 gene in muscle progenitor cell migration and neuronal determination processes. Three susceptibility loci (rs11190870, rs625039, and rs11598564) near the LBX1 gene, as well as another susceptibility locus (rs678741), related to LBX1 regulation, have been successfully verified to have robust associations with AIS in multi-ethnic populations. The LBX1 gene plays an essential role in regulating the migration and proliferation of muscle precursor cells, and it is known to play a role in neuronal determination processes, especially for the fate of somatosensory relay neurons. The LBX1 gene is the most promising candidate gene in AIS susceptibility due to its position and possible functions in muscle progenitor cell migration and neuronal determination processes. The causality between susceptibility loci related to the LBX1 gene and the pathogenesis of AIS deserves to be explored with further integrated genome-wide and epigenome-wide association studies.

Highlights

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity, defined as a lateral spinal curvature with a Cobb angle of >10 degrees, and it affects millions of children worldwide (Cheng et al, 2015)
The association of the four variants related to LBX1 with AIS severity failed to be replicated. These results suggested that the LBX1 gene might be involved in the initiation but not in the progression of AIS
A chromosome conformation capture assay revealed that the genome region with the most significantly associated SNP physically interacted with the promoter region of LBX1, and the risk allele showed higher transcriptional activity in HEK 293T cells (Guo et al, 2016). These results suggest that rs11190870 confers AIS susceptibility by upregulating LBX1 transcription

Summary

Introduction

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity, defined as a lateral spinal curvature with a Cobb angle of >10 degrees, and it affects millions of children worldwide (Cheng et al, 2015). Genome-wide association studies (GWASs) have identified many susceptibility loci as well as candidate genes such as ER1, PAX1, LBX1, GPR126, and SLC39A8 (Takahashi et al, 2011; Kou et al, 2013; Zhu et al, 2015; Haller et al, 2018). Replication studies for most susceptibility loci are hard to verify these associations in multi-ethnic populations. LBX1 Gene in Adolescent Idiopathic Scoliosis the robust significant association of rs11190870 in Asian and Caucasian AIS patients (Cao et al, 2016; Jiang et al, 2019).

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