青少年特发性脊柱侧凸(AIS)发病原因不明，遗传因素及肌肉发育在其发生过程中起着重要作用。本课题组前期完成首个汉族AIS人群的全基因组关联分析研究（GWAS），首次发现位于2q36.1的PAX3基因附近的rs13398147与AIS发病具有显著相关性。PAX3通过调控生肌调节因子，在脊柱的轴下肌的形成、迁移等过程中具有重要作用，我们前期研究也发现AIS患者存在椎旁肌发育异常。由此，我们推测PAX3通过生肌调节因子调控椎旁肌发育，在AIS发病中发挥作用。本项目拟检测AIS患者PAX3异常表达并分析其与临床表型（畸形程度、肌肉发育等）之间的相关性，进而探究可影响PAX3表达的功能性易感位点及其调控机制，最后通过细胞实验、动物实验研究PAX3通过生肌调节因子对肌肉发育的潜在影响，揭示其在AIS发病中的作用。研究成果将有助于进一步理解AIS发病机制，为开展AIS分子治疗奠定理论基础。

The etiology of adolescent idiopathic scoliosis (AIS) remains unknown. Genetic factors and paravertebral muscle development play important role in the occurrence of AIS. Recently we have completed the first genome-wide association study of AIS in Chinese Han population, and we first found the SNP rs13398147 significantly associated with AIS, is located in PAX3. PAX3 is essential for the formation and migration of the inferior axis muscles of the spine via myogenic regulatory factors. Moreover, our previous study found abnormalities in paravertebral muscle for AIS patients. We therefore speculated that PAX3 could play a role in the etiology of AIS through regulation of paravertebral muscle development via myogenic regulatory factors. In this project, we plan to detect the abnormal expression of PAX3 in AIS, and analyze the relationship between the expression of PAX3 and clinical phenotype of AIS patients, such as deformity severity, spinal muscles volume and strength. We further pinpoint the functional SNPs that can influence the expression of PAX3. Finally, the cell experiment and animal model are to be used to investigate the functional role of PAX3 on the development of spinal muscles. We believe this project can expand our understanding on the etiology of AIS, and lay a theoretical foundation for the molecular therapy of AIS.