Association Of SPRY4 And RUNX2 Gene Polymorphisms With Adolescent Idiopathic Scoliosis And PUMC Type

BackgroundAdolescent Idiopathic Scoliosis(AIS)affects 1-3%of the population,but its pathogenesis is unknown.At present,Lenke and PUMC type are mainly used in clinic.Yong Qiu et al.compared the reliability and repeatability of three classification systems,it is proved that PUMC classification includes the deformed features of scoliosis in the threedimensional plane,the classification is comprehensive,easy to master,and has good reliability and repeatability,which is suitable for three-dimensional correction of scoliosis.Li et al.found that SPRY4 is involved in the pathogenesis of adolescent idiopathic scoliosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells and melatonin response.Depletion of SPRY4 in bone marrow-derived mesenchymal stem cells leads to reduced osteogenic differentiation,and these defects are further aggravated under the influence of melatonin,providing new insights into the role of melatonin in AIS etiology.The total expression of Runx2 protein and Runx2 mRNA in the convex and concave growth plates of the vertebral body was significantly different.RNA and protein analysis showed low Runx2 levels in the cancellous bone of adolescent idiopathic scoliosis.The abnormal expression of Runx2 and decreased BMD in adolescents with idiopathic scoliosis indicate abnormal regulation of osteoblast differentiation,suggesting that Runx2 may play an important role in the pathogenesis of decreased BMD in adolescents with idiopathic scoliosis.Therefore,SPRY4&RUNX2 genes play a significant role in adolescent idiopathic scoliosis.Objects1.To explore the single nucleotide polymorphism loci associated with AIS in SPRY4&RUNX2 genes.2.Combined with PUMC classification,subgroup analysis was performed to explore the clinical application value.MethodsPatients of Northern Han nationality(Shandong,Hebei,Shanxi,Beijing,Tianjin,Henan,etc.)treated in our hospital were selected.From December 2017 to December 2021,a total of 97 patients diagnosed with AIS from the Han Chinese population and 100 healthy internal subjects from Peking Union Medical College Hospital were enrolled in the DISCO(Deciphering Disorders Involving Scoliosis and Comorbidities)study.Signed informed consent forms were obtained from all participants or their parents.The ethics committee of Peking Union Medical College Hospital and the Chinese Academy of Medical Sciences approved the study.The whole genome DNA of patients and control samples was extracted,and the SNP gene was categorized.Plink and SPSS were used for statistical analysis.Combined with PUMC typing,subgroup analysis of loci was performed to determine the clinical subgroup phenotype associated with the genotype.Results1.two SNPs in each SPRY4&RUNX2 gene were selected.2.SPRY4 rs3797053 allele and genotype were not significantly different in Chinese Han adolescent idiopathic scoliosis group compared with healthy group(P=0.245,P=0.499).The frequency of SPRY4 rs10040443 C allele in AIS group was significantly higher than that in healthy group(17.5%vs 8.0%,P=0.005),and there was a statistical difference between CC genotype and healthy group(P=0.014).The genotype distribution of this locus in AIS was correlated with PUMC typing(P=0.001),and its genotype C/T+T/T was correlated with the incidence of PUMC Ⅱ patients.3.The RUNX2 rs1321075 TT genotype was significantly different in the Han adolescent idiopathic scoliosis group in northern China compared with the healthy group(P=3.003),but there was no significant difference in allele frequency between the AIS group and the healthy group(P=0.866).The genotype distribution of this locus in AIS group was correlated with PUMC typing(P=0.011),and its genotype G/G+T/G was correlated with the incidence of PUMC Ⅲ patients.rs 1406846 alleles and genotypes were not significantly different from those of healthy groups(P=0.196,P=0.252).Conclusions1.The rs10040443 site of SPRY4 gene and rs1321075 site of RUNX2 gene were associated with AIS in the Han population in northern China.2.SPRY4 gene rs10040443 has been associated with adolescent idiopathic scoliosis in the Han population of northern China,and the C allele may be a risk factor for the disease.The RUNX2 gene rs1321075 is associated with adolescent idiopathic scoliosis in the Han population of northern China,and the TT genotype may be a risk factor for adolescent idiopathic scoliosis.3.SPRY4&RunX2-susceptible SNPS are associated with PUMC type system,which may have potential clinical value.In the future,cell animal experiments should be combined to verify whether they are functional loci.