Department of Spine Surgery, the Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing and Hong Kong, China.
Spine (Phila Pa 1976). 2021 Nov 15;46(22):E1178-E1184. doi: 10.1097/BRS.0000000000004098.
A genetic case-control study.
To investigate whether the variants in BOC, SEC16B, and SH2D1B are sex-specifically and functionally associated with the susceptibility of adolescent idiopathic scoliosis (AIS) in Chinese Han population.
A recent genome-wide association study identified three female-specific susceptibility loci of AIS in Japanese population. However, the association of these genes with AIS in other populations remains unclear. Further investigation of the functional role of the three genes was warranted.
SNPs rs73235136, rs545608, and rs142502288 were genotyped in 1599 AIS patients and 2985 controls. Paraspinal muscle collected from 40 AIS and 30 lumber disc herniation patients during surgical interventions was used for gene expression analysis. The difference regarding genotype and allele frequency between patients and controls was analyzed by chi-square analysis. Expression of BOC and SEC16B was compared between AIS and lumber disc herniation patients by the Student t test. Pearson correlation analysis was performed to evaluate the relationship between gene expression level and clinical phenotypes.
SNPs rs73235136 of BOC and rs545608 of SEC16B were found to be remarkably associated with AIS only in females. Allele C of rs73235136 and allele G of rs545608 could significantly add to the risk of female AIS patients, with an odds ratio of 1.087 and 1.033, respectively. However, there was no significant difference between the male patients and controls regarding genotype or allele frequency of rs73235136 and rs545608. No polymorphism at rs142502288 was detected in either patients or controls, and all the subjects had genotype of AA. Moreover, tissue expression of BOC and SEC16B was significantly lower in AIS patients compared with controls. BOC expression was positively associated with bone mineral contents, and expression of SEC16B was negatively correlated with curve severity in AIS patients.
Female-specific variants in BOC and SEC16B were associated with AIS. Expression of BOC and SEC16B was significantly lower in AIS patients. The role of BOC and SEC16B in the development of AIS is worthy of further investigation.Level of Evidence: 3.
一项遗传病例对照研究。
探讨 BOC、SEC16B 和 SH2D1B 中的变异是否与中国汉族青少年特发性脊柱侧凸（AIS）的易感性存在性别特异性和功能相关性。
最近的全基因组关联研究在日本人群中发现了三个女性特异性的 AIS 易感位点。然而，这些基因与其他人群中 AIS 的关联尚不清楚。有必要进一步研究这三个基因的功能作用。
在 1599 例 AIS 患者和 2985 例对照中对 rs73235136、rs545608 和 rs142502288 进行了基因分型。在手术干预期间，从 40 例 AIS 和 30 例腰椎间盘突出症患者的脊柱旁肌肉中采集了组织，用于基因表达分析。通过卡方检验分析患者和对照组之间基因型和等位基因频率的差异。通过学生 t 检验比较 AIS 患者和腰椎间盘突出症患者的 BOC 和 SEC16B 表达。进行皮尔逊相关分析以评估基因表达水平与临床表型的关系。
仅在女性中发现 BOC 的 rs73235136 和 SEC16B 的 rs545608 显著与 AIS 相关。rs73235136 的等位基因 C 和 rs545608 的等位基因 G 可显著增加女性 AIS 患者的患病风险，比值比分别为 1.087 和 1.033。然而，男性患者与对照组在 rs73235136 和 rs545608 的基因型或等位基因频率方面无显著差异。在患者或对照组中均未检测到 rs142502288 的多态性，所有受试者均为 AA 基因型。此外，AIS 患者的 BOC 和 SEC16B 组织表达明显低于对照组。BOC 表达与骨矿物质含量呈正相关，而 SEC16B 表达与 AIS 患者的曲线严重程度呈负相关。
BOC 和 SEC16B 中的女性特异性变异与 AIS 相关。AIS 患者的 BOC 和 SEC16B 表达明显降低。BOC 和 SEC16B 在 AIS 发病机制中的作用值得进一步研究。
3 级。
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