MIR4300HG 的遗传变异与中国人群青少年特发性脊柱侧凸的进展相关。

Genetic variant of MIR4300HG is associated with progression of adolescent idiopathic scoliosis in a Chinese population.

机构信息

Department of Spine Surgery, Drum Tower Hospital Clinical College of Nanjing Medical University, Zhongshan Road 321, Nanjing, 210008, China.

Department of Spine Surgery, Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

出版信息

J Orthop Surg Res. 2021 May 13;16(1):311. doi: 10.1186/s13018-021-02455-w.

DOI:10.1186/s13018-021-02455-w

PMID:33985553

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8117547/

Abstract

BACKGROUND

A recent genome-wide association study identified a susceptible locus in MIR4300HG gene that was associated with curve progression of adolescent idiopathic scoliosis (AIS) in the Japanese population. However, the association between the gene and curve progression in other populations remains unclear.

METHODS

A cohort of 1952 AIS patients and 2495 healthy controls were included in the case-control analysis. In the case-only analysis, 747 patients were assigned to the progression group and 520 patients were assigned to the non-progression group, respectively. Rs35333564 was genotyped for all the subjects. Paraspinal muscles of 76 patients were collected for the analysis of gene expression. Chi-square test and ANOVA test were used for the intergroup comparison. Pearson correlation analysis was performed to investigate the relationship between the gene expression and curve magnitude.

RESULTS

Variant rs35333564 was significantly associated with the curve severity of AIS (p = 0.025), but not the development of AIS (p = 0.418). Genotype GG was indicated by remarkably lower expression of MIR4300 (p = 0.020) which was significantly correlated with curve magnitude (p = 0.010). As a predicted target gene of MIR4300, the expression of CRTC1 was negatively correlated with MIR4300 expression (p = 0.012, r = -0.287) and positively correlated with curve severity (p = 0.025, r = 0.257).

CONCLUSIONS

The association between rs35333564 and curve progression was successfully replicated in a Chinese AIS population. CRTC1 may be the target gene of MIR4300 that plays a role in the curve progression of AIS.

摘要

背景

最近的全基因组关联研究在 MIR4300HG 基因中发现了一个易感位点，该位点与日本人群青少年特发性脊柱侧凸（AIS）的曲线进展有关。然而，该基因与其他人群的曲线进展之间的关联尚不清楚。

方法

本病例对照分析纳入了 1952 例 AIS 患者和 2495 例健康对照。在仅病例分析中，747 例患者被分配到进展组，520 例患者被分配到非进展组。对所有受试者进行 rs35333564 基因分型。收集 76 例患者的椎旁肌进行基因表达分析。采用卡方检验和方差分析进行组间比较。采用 Pearson 相关分析探讨基因表达与曲线幅度的关系。

结果

变异 rs35333564 与 AIS 的曲线严重程度显著相关（p = 0.025），但与 AIS 的发生无关（p = 0.418）。基因型 GG 表现出 MIR4300 表达显著降低（p = 0.020），与曲线幅度显著相关（p = 0.010）。作为 MIR4300 的预测靶基因，CRTC1 的表达与 MIR4300 表达呈负相关（p = 0.012，r = -0.287），与曲线严重程度呈正相关（p = 0.025，r = 0.257）。