The Role And Function Of Susceptible Genes In AIS

Chapter 2 The Role of Dipeptidyl Peptidase-4 in Adolescent Idiopathic Scoliosis Development: Expression in MyoblastsObjective.To investigate the influence of dipeptidyl peptidase-4(DPP-4)on the biological viability of myoblasts extracted from adolescent idiopathic scoliosis(AIS)patients and to further characterize its role in the development of AIS.Summary of background data.AIS girls were prone to have a taller stature with lower body mass index(BMI)probably due to the abnormal energy homeostasis.DPP-4 can regulate energy homeostasis,insulin secretion and sensitivity directly or indirectly by controlling GLP-1 inactivation.Methods.Circulation DPP-4 level was assessed in serum of 54 AIS girls,24 age,sex and curve-matched congenital scoliosis(CS)patients and 24 healthy controls by ELISA.Myoblasts were derived from muscle specimens of AIS and CS patients.Cells were treated with glucose and insulin.Gene and protein expressions were evaluated by RT-q PCR and Western blot.Results.Our outcomes illustrated the DPP-4 expression in circulation in AIS girls was 0.76 times that of healthy controls,respectively(p = 0.0075).Similarly,the results of muscular tissue have revealed that the DPP-4 gene and protein expression AIS girls was 0.68 and 0.54 times as much as CS patients,respectively(p = 0.0074,p = 0.0085).Conclusions.The present study revealed divergence in DPP-4 expression levels,and the modulation of DPP-4 and insulin-related signal transduction via a different manner in myoblasts isolated from AIS participants compared to CS patients.Chapter 3 The association between CELSR2 gene and the susceptibility of adolescent idiopathic scoliosis in the Chinese populationObjectives To validate the association between the CELSR2 gene and the susceptibility of adolescent idiopathic scoliosis(AIS)in the Chinese population.Methods Allelic specific multiple ligase detection reactions were used to detect the genotyping of rs141489111,rs6698843 and rs2281894 in 1794 AIS patients and 1040 normal controls.The genotyping information of other single nucleotide polymorphism sites(SNPs)of the CELSR2 gene was analyzed based on the GWAS database we previously published.The paravertebral muscles of 45 AIS patients and 10 age-matched spinal trauma(Control)patients were collected during the operation which were used to evaluate the expression tissue of CELSR2.The Student's t test was used to compare CELSR2 expression level and clinic characterists between AIS patients and the controls.Genotyping information were analyzed through Chi-square test.Results No mutation was detected in the rs141489111 locus of patients or controls and all subjects had homozygous genotype GG.The genotypes and allele frequencies of rs6698843 and rs2281894 were not significantly different between the two groups.The GWAS database showed that there is no significant difference regarding genotypes or allele frequencies of other seven SNP loci located in the CELSR2 gene between the two groups.Moreover,m RNA expression of CELSR2 in AIS patients is comparable with that in the controls.Conclusion Our large-scale replication study of the variants in CELSR2 gene did not support its association with the susceptibility of AIS in the Chinese population.CELSR2 may be not included in the onset of AIS in Chinese population.