A Functional SNP in the Promoter of LBX1 Is Associated With the Development of Adolescent Idiopathic Scoliosis Through Involvement in the Myogenesis of Paraspinal Muscles.

Leilei Xu,Zhen Liu,Nelson Tang,Xu Sun,Zhenhua Feng,Zhichong Wu,Yong Qiu,Wayne Y W Lee,Zezhang Zhu,Zhicheng Dai,Jack Chun-Yiu Cheng

doi:10.3389/fcell.2021.777890

Abstract

Previous studies have shown that LBX1 is associated with adolescent idiopathic scoliosis (AIS) in multiple populations. For the first time, rs1322330 located in the putative promoter region of LBX1 was found significantly associated with AIS in the Chinese population [p = 6.08 × 10–14, odds ratio (OR) = 1.42, 95% confidence interval of 1.03–1.55]. Moreover, the luciferase assay and electrophoretic mobility shift assay supported that the allele A of rs1322330 could down-regulate the expression of LBX1 in the paraspinal muscles of AIS. In addition, silencing LBX1 in the myosatellite cells resulted in significantly inhibited cell viability and myotube formation, which supported an essential role of LBX1 in muscle development of AIS. To summarize, rs1322330 may be a novel functional SNP regulating the expression of LBX1, which was involved in the etiology of AIS possibly via regulation of myogenesis in the paraspinal muscles.

Highlights

As a multifactorial disease, the etiology of adolescent idiopathic scoliosis (AIS) remains poorly understood (Murray and Bulstrode, 1996; Kouwenhoven and Castelein, 2008)
Through fine-mapping of a 40-kb region surrounding rs11190870, we pinpointed a potentially functional single-nucleotide polymorphism (SNP) rs1322330 located in the promoter region of LBX1
Based on a large independent cohort of patients and controls, we further confirmed that rs1322330 was remarkably associated with the development of Chinese AIS

Summary

Introduction

The etiology of adolescent idiopathic scoliosis (AIS) remains poorly understood (Murray and Bulstrode, 1996; Kouwenhoven and Castelein, 2008). It was speculated that AIS could be a complex polygenic disease influenced by different loci. Following this speculation, genetic factors have been extensively investigated in the past decades. Genomewide linkage analysis and candidate gene association studies were applied to unveil the genetic background of AIS (Miller et al, 1996; Inoue et al, 2002; Morcuende et al, 2003; Liu et al, 2010). Both methods had low efficiency to provide accurate and replicable results (Takahashi et al, 2011b)

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