Zhang Zheng, Zhang Zhanrong, Shu Lun, Meng Yichen, Ma Jun, Gao Rui, Zhou Xuhui
Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai.
Department of Orthopedics, Hainan Hospital, Chinese PLA General Hospital, Hainan, People's Republic of China.
Spine (Phila Pa 1976). 2023 Jan 15;48(2):E20-E24. doi: 10.1097/BRS.0000000000004484. Epub 2022 Sep 20.
A case-control association study.
This study aimed to reveal whether mutations within roundabout receptor 3 ( ROBO3 ) gene were related to adolescent idiopathic scoliosis (AIS) in Chinese Han population and to investigate the functional role of ROBO3 in the pathogenesis and progression of AIS.
ROBO3 is essential for the regulation of hindbrain axonal cell migration and midline crossing. Studies have demonstrated that ROBO3 homozygous mutations are associated with horizontal gaze palsy with progressive scoliosis. However, whether and how ROBO3 contributed to the development of scoliosis remains unclear.
Whole exome sequencing was performed in 135 AIS patients and 267 healthy controls to evaluate the differences of single nucleotide polymorphism variants within ROBO3 . Then the identified variant of ROBO3 was genotyped in another cohort included 1140 AIS patients and 1580 controls. Moreover, paraspinal muscles were collected from 39 AIS patients and 45 lumbar disk herniation patients for the measurement of ROBO3 mRNA expression. The χ 2 test, Fisher exact test or the Student t test were used to compare intergroup data. Pearson correlation was used to determine the association between ROBO3 expression and clinical phenotypes.
A significant association was identified between the gene variant (rs74787566) of ROBO3 and the development of AIS through exome sequencing. The genotyping cohort demonstrated a higher frequency of allele A in AIS patients compared to controls (7.89% vs . 4.30%, P <0.001, odds ratio=1.87). In addition, the expression of ROBO3 in paraspinal muscles was inversely correlated with the Cobb angle ( P =0.043, r2 =0.1059).
A significant association was identified between the gene variant (rs74787566) of ROBO3 and the development of AIS. The reduced expression of ROBO3 could result in the progression of curve magnitude in patients with AIS. Further studies are needed to verify the functional role of ROBO3 in the development of AIS.
Level III.
一项病例对照关联研究。
本研究旨在揭示在中国汉族人群中，迂回受体3（ROBO3）基因内的突变是否与青少年特发性脊柱侧凸（AIS）相关，并探讨ROBO3在AIS发病机制和进展中的功能作用。
ROBO3对后脑轴突细胞迁移和中线交叉的调节至关重要。研究表明，ROBO3纯合突变与进行性脊柱侧凸伴水平凝视麻痹相关。然而，ROBO3是否以及如何导致脊柱侧凸的发生仍不清楚。
对135例AIS患者和267例健康对照进行全外显子组测序，以评估ROBO3内单核苷酸多态性变异的差异。然后，在另一个包含1140例AIS患者和1580例对照的队列中对鉴定出的ROBO3变异进行基因分型。此外，从39例AIS患者和45例腰椎间盘突出症患者中采集椎旁肌肉，用于测量ROBO3 mRNA表达。采用χ²检验、Fisher精确检验或Student t检验比较组间数据。采用Pearson相关性分析确定ROBO3表达与临床表型之间的关联。
通过外显子组测序发现ROBO3基因变异（rs74787566）与AIS的发生之间存在显著关联。基因分型队列显示，AIS患者中A等位基因的频率高于对照组（7.89%对4.30%，P<0.001，比值比=1.87）。此外，ROBO3在椎旁肌肉中的表达与Cobb角呈负相关（P=0.043,r²=0.1059）。
ROBO3基因变异（rs74787566）与AIS的发生之间存在显著关联。ROBO3表达降低可能导致AIS患者的侧弯程度进展。需要进一步研究来验证ROBO3在AIS发生中的功能作用。
三级。
