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

doi:10.3389/fcell.2021.777890

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

Front Cell Dev Biol. 2021 Nov 30:9:777890. doi: 10.3389/fcell.2021.777890. eCollection 2021.

Authors

Leilei Xu^{1

2}, Zhenhua Feng^{1

2}, Zhicheng Dai^{1

2}, Wayne Y W Lee^{2

3

4}, Zhichong Wu^{1

2}, Zhen Liu^{1

2}, Xu Sun^{1

2}, Nelson Tang^{2

3

5}, Jack Chun-Yiu Cheng^{2

3}, Yong Qiu^{1

2}, Zezhang Zhu^{1

2}

Affiliations

¹ Division of Spine Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
² Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing/Hong Kong, China.
³ SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
⁴ Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
⁵ Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.

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.

Keywords: LBX1 gene; adolescent idiopathic scoliosis (AIS); gene variant; myogenesis; paraspinal muscle.

Associated data

figshare/10.6084/m9.figshare.16864672