Department of Spine Surgery, the Affiliated 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). 2018 Apr 1;43(7):492-496. doi: 10.1097/BRS.0000000000002475.
A genetic association study.
To investigate the association between PAX1 gene and the susceptibility of adolescent idiopathic scoliosis (AIS) in the Chinese population and to further determine the functional variant regulating PAX1 expression in patients with AIS.
In a previous study an enhancer locus of PAX1 was reported to be associated with the development of AIS in the Caucasian and the Japanese population. However, there is a paucity of knowledge concerning the functional role of PAX1 in the Chinese AIS population.
The single-nucleotide polymorphisms rs6137473 and rs169311 were genotyped in 2914 patients and 3924 controls. The differences of genotype and allele distributions between patients and controls were calculated using chi-square test. Paraspinal muscles were collected from 84 patients with AIS. The one-way analysis of variance test was used to compare the mRNA expression of PAX1 among different genotypes.
Both rs6137473 and rs169311 were significantly associated with the susceptibility of AIS. Allele G of rs6137473 and allele A of rs169311 can significantly add to the risk of AIS with an odds ratio of 1.17 and 1.22, respectively. Moreover, there was significant difference regarding the expression of the PAX1 between the concave side and convex side of the patients. Patients with genotype AA of rs169311 had significantly decreased expression of PAX1 than those with genotype CC. As for rs6137473, no remarkable difference of PAX1 expression was found among the three genotypes.
The association between PAX1 and the susceptibility of AIS was successfully replicated in the Chinese population. Moreover, rs169311 could be a functional variant regulating the expression of PAX1 in the paraspinal muscles of AIS. Further functional analysis is warranted for a comprehensive knowledge on the contribution of this variant to the development of AIS.
一项遗传关联研究。
探讨中国人 PAX1 基因与青少年特发性脊柱侧凸（AIS）易感性的关系，并进一步确定调节 AIS 患者 PAX1 表达的功能变异。
先前的一项研究报道，PAX1 的增强子位点与白种人和日本人群的 AIS 发展有关。然而，关于 PAX1 在中国人 AIS 人群中的功能作用知之甚少。
在 2914 例患者和 3924 例对照中，对单核苷酸多态性 rs6137473 和 rs169311 进行了基因分型。使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。从 84 例 AIS 患者中采集脊柱旁肌肉。使用单因素方差分析比较不同基因型之间 PAX1 的 mRNA 表达。
rs6137473 和 rs169311 均与 AIS 的易感性显著相关。rs6137473 的等位基因 G 和 rs169311 的等位基因 A 可分别显著增加 AIS 的发病风险，比值比分别为 1.17 和 1.22。此外，患者的凹侧和凸侧之间的 PAX1 表达存在显著差异。rs169311 的基因型 AA 的患者的 PAX1 表达明显低于基因型 CC 的患者。对于 rs6137473，三种基因型之间的 PAX1 表达无显著差异。
PAX1 与 AIS 易感性的关联在中国人中得到了成功复制。此外，rs169311 可能是调节 AIS 脊柱旁肌肉中 PAX1 表达的功能变异。需要进一步的功能分析，以全面了解该变异对 AIS 发展的贡献。
3 级。
