新证据支持 FBN1 在青少年特发性脊柱侧凸发展中的作用。
New Evidence Supporting the Role of FBN1 in the Development of Adolescent Idiopathic Scoliosis.
机构信息
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, Hong Kong, China.
出版信息
Spine (Phila Pa 1976). 2019 Feb 15;44(4):E225-E232. doi: 10.1097/BRS.0000000000002809.
STUDY DESIGN
A genetic association study.
OBJECTIVE
To determine whether common variants of fibrillin-1 (FBN1) and fibrillin-2 (FBN2) are associated with adolescent idiopathic scoliosis (AIS), and to further investigate to further investigate the functional role of FBN1 in the onset and progression of AIS.
SUMMARY OF BACKGROUND DATA
Previous studies have identified several rare variants in FBN1 and FBN2 that were associated with AIS. There is, however, a lack of knowledge concerning the association between common variants of FBN1 and FBN2 and AIS.
METHODS
Common variants covering FBN1 and FBN2 were genotyped in 952 patients with AIS and 1499 controls. Paraspinal muscles were collected from 66 patients with AIS and 18 patients with lumbar disc herniation (LDH) during surgical interventions. The differences of genotype and allele distributions between patients and controls were calculated using Chi-square test. The Student t test was used to compare the expression of FBN1 and FBN2 between patients with AIS and LDH. One-way analysis of variance test was used to compare the gene expression among different genotypes of the significantly associated variant. The Pearson correlation analysis was used to determine the relationship between FBN1 expression and the curve severity.
RESULTS
The common variant rs12916536 of FBN1 was significantly associated with AIS. Patients were found to have significantly lower frequency of allele A than the controls (0.397 vs. 0.450, P = 1.10 × 10) with an odds ratio of 0.81. Moreover, patients with AIS were found to have significantly lower FBN1 expression than patients with LDH (0.00033 ± 0.00015 vs. 0.00054 ± 0.00031, P = 1.70 × 10). The expression level of FBN1 was remarkably correlated with the curve severity (r = -0.352, P = 0.02). There was no significant difference of FBN1 expression among different genotypes of rs12916536.
CONCLUSION
Common variant of FBN1 is significantly associated with the susceptibility of AIS. Moreover, the decreased expression of FBN1 is significantly correlated with the curve severity of AIS. The functional role of FBN in AIS is worthy of further investigation.
LEVEL OF EVIDENCE
研究设计
一项遗传关联研究。
目的
确定原纤维蛋白 1（FBN1）和原纤维蛋白 2（FBN2）的常见变体是否与青少年特发性脊柱侧凸（AIS）相关，并进一步研究 FBN1 在 AIS 的发病和进展中的功能作用。
背景资料概要
先前的研究已经确定了 FBN1 和 FBN2 中的几个与 AIS 相关的罕见变体。然而，对于 FBN1 和 FBN2 的常见变体与 AIS 之间的关联，我们知之甚少。
方法
在 952 名 AIS 患者和 1499 名对照中对 FBN1 和 FBN2 进行常见变体基因分型。在手术干预期间，从 66 名 AIS 患者和 18 名腰椎间盘突出症（LDH）患者的脊柱旁肌肉中收集。使用卡方检验计算患者与对照组之间基因型和等位基因分布的差异。使用 Student t 检验比较 AIS 患者与 LDH 患者之间 FBN1 和 FBN2 的表达差异。使用单因素方差分析检验显著相关变异的不同基因型之间的基因表达差异。使用 Pearson 相关分析确定 FBN1 表达与曲线严重程度之间的关系。
结果
FBN1 的常见变体 rs12916536 与 AIS 显著相关。与对照组相比，患者的等位基因 A 频率明显较低（0.397 对 0.450，P=1.10×10），优势比为 0.81。此外，与 LDH 患者相比，AIS 患者的 FBN1 表达明显较低（0.00033±0.00015 对 0.00054±0.00031，P=1.70×10）。FBN1 的表达水平与曲线严重程度呈显著负相关（r=-0.352，P=0.02）。rs12916536 的不同基因型之间 FBN1 的表达水平无显著差异。
结论
FBN1 的常见变体与 AIS 的易感性显著相关。此外，FBN1 表达的降低与 AIS 的曲线严重程度显著相关。FBN 在 AIS 中的功能作用值得进一步研究。
证据水平
3 级。
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