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

Yuwen Wang,Zhicheng Dai,Zhen Liu,Zhichong Wu,Xu Sun,Zezhang Zhu,Zhenhua Feng,Yong Qiu,Leilei Xu

doi:10.1186/s13018-021-02455-w

Abstract

BackgroundA 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.MethodsA 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.ResultsVariant 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).ConclusionsThe 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.

Highlights

Adolescent idiopathic scoliosis (AIS) is a complex spinal deformity that affects 2–3% of children aged 10–16 years worldwide [1]
The purpose of the present study was to validate the association of MIR4300HG with the progression of adolescent idiopathic scoliosis (AIS) and to further determine the target gene of MIR4300 that may be involved in the curve progression
Considering histochemical and physiological abnormalities in muscles of patients with idiopathic scoliosis [21], we suggested that CRTC1 may be the target gene of MIR4300 that may function in the curve progression

Summary

Introduction

Adolescent idiopathic scoliosis (AIS) is a complex spinal deformity that affects 2–3% of children aged 10–16 years worldwide [1]. The component SNPs of ScoliScore were not successfully replicated in the Chinese, the CanadianFrench, or the Japanese population, implying the importance of validation study when embedding new genetic markers in the predictive model of curve progression [11,12,13,14]. Ogura et al [15] conducted a GWAS study and identified that a functional variant rs35333564, located in the host gene of microRNA MIR4300 (MIR4300HG), was associated with progression of AIS. The purpose of the present study was to validate the association of MIR4300HG with the progression of AIS and to further determine the target gene of MIR4300 that may be involved in the curve progression. 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. The association between the gene and curve progression in other populations remains unclear

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