Genetic Variant of TBX1 Gene Is Functionally Associated With Adolescent Idiopathic Scoliosis in the Chinese Population
Genetic Variant of TBX1 Gene Is Functionally Associated With Adolescent Idiopathic Scoliosis in the Chinese Population
复制标题
TBX1 基因的遗传变异与中国人群中青少年特发性脊柱侧弯存在功能相关性。
DOI：
10.1097/brs.0000000000003700
复制
发表时间：
2021-01-01
期刊：
影响因子：
3
通讯作者：
Zhu, Zezhang
中科院分区：
文献类型：
--
作者：
Li, Yang;Wu, Zhichong;Zhu, Zezhang
研究设计
遗传关联研究目的：探讨TBX 1基因rs 1978060位点是否为中国汉族青少年特发性脊柱侧凸（AIS）的易感基因，进一步明确TBX 1在AIS发生发展中的作用。
背景资料概述
最近的一项全基因组关联研究报告了TBX 1基因中的一个新的易感位点，该位点与日本人群中AIS的发生相关。然而，关于TBX 1在中国AIS人群中的功能作用的知识很少。
方法
对1725名女性AIS患者和2600名健康对照者进行SNP rs 1978060基因分型。从30名AIS患者和26名年龄匹配的先天性脊柱侧凸（CS）患者中收集椎旁肌肉样本用于组织表达分析。采用卡方检验计算患者和对照组之间基因型和等位基因分布的差异。采用Pearson相关分析探讨PAX 1基因表达与弯曲程度的关系。
结果
SNP rs 1978060与AIS的易感性显著相关。rs 1978060的等位基因G可显著增加AIS的风险，比值比为1.12。AIS患者TBX 1的组织表达明显降低。TBX 1表达与曲线幅度呈显著正相关（r =-0.519，p = 0.003）。
结论
TBX 1与AIS易感性之间的关联在中国人群中被成功复制。此外，rs 1978060可能是调节TBX 1表达的功能性变体。TBX 1在AIS发病和进展中的作用有待进一步研究。
证据等级
3.
STUDY DESIGN
A genetic association study OBJECTIVE.: To investigate whether rs1978060 of TBX1 gene was a susceptible locus of adolescent idiopathic scoliosis (AIS) in the Chinese Han population and to better define the functional role of TBX1 in the development and progression of AIS.
SUMMARY OF BACKGROUND DATA
A recent genome-wide association study reported a novel susceptible locus in TBX1 gene which was associated with the development of AIS in the Japanese population. However, there is a paucity of knowledge concerning the functional role of TBX1 in the Chinese AIS population.
METHODS
The SNP rs1978060 was genotyped in 1725 female AIS patients and 2600 healthy controls. Paraspinal muscle samples were collected from 30 AIS patients and 26 age-matched congential scoliosis (CS) patients for the analysis of tissue expression. The differences of genotype and allele distributions between the patients and the controls were calculated using the Chi-square test. The Pearson correlation analysis was carried out to investigate the relation between the expression of the PAX1 gene and the curve severity.
RESULTS
SNP rs1978060 was significantly associated with the susceptibility of AIS. Allele G of rs1978060 could significantly add to the risk of AIS with an odds ratio of 1.12. The tissue expression of TBX1 was obviously decreased in AIS patients. There was a remarkable correlation between the curve magnitude and the TBX1 expression (r = -0.519, p = 0.003).
CONCLUSION
The association between TBX1 and the susceptibility of AIS was successfully replicated in the Chinese population. Moreover, rs1978060 may be a functional variant regulating the expression of TBX1. More studies were warranted to explore the functional role of TBX1 in the onset and progression of AIS.
LEVEL OF EVIDENCE
3.