Study On The Association Between Gene Polymorphism And Adolescent Idiopathic Scoliosis In Chinese Han Population

IntroductionAdolescent Idiopathic Scoliosis (AIS) is the most common type of scoliosis and the incidence ranges from 0.47% to 5.2% among different races. People found that the risk for the first degree relatives of AIS patients increased obviously. We haven’t locate a single gene through years of research. In recent years, many research teams focused on the Single Nucleotide Polymorphism (SNP) and they have already screened 39 candidate genes including IGF-1, ESR1, LBX-1, GPR126 and so on. However, those studies have many defects. The sample size differs between each research team. Some small one have only dozens of patients so the confidence level of their result still need discussion. Result coming from one race sometime couldn’t be replicated in another. There’s no large cohort of Northern Chinese Han so we can’t use other team’s work directly. Finally, little functional study was applied so the results are still’association’not’pathogenic’. So we need replicate reported SNP sites in our cohort and apply further functional study in some important candidate gene.Objective1. Build a genetic study cohort of AIS in Northern Chinese Han population.2. Perform replication study of reported AIS associate SNPs in this cohort.3. Design functional study for the most important candidate gene and try to explain its pathogenic mechanism.MethodsSet the inclusion and exclusion criteria, collect the peripheral blood sample and clinical data of AIS patients who receive surgery in PUMC hospital. Review the lectures about SNP study in AIS and confirm the target SNP sites. Genotyping the SNP of patients and health control by Sequenom MassArray system. Analysis the results using PUNK and SPSS software. Among the candidate genes, LBX1 is the most important one so we perform association study in this gene by Sequenom MassArray system. For the chosen candidate site we study its function by dual luciferase system.Results1. In this study we include 180 AIS patients from Northern Chinese Han population and 182 matched healthy control.2. After reviewing lectures we select 20 AIS associate SNPs such as rs1065755.3. Rs11190870, rsl2885713 and rs2300500 are associate with AIS in allele, genotype and genetic model analysis. Rs6570507 and rs4753426 are associate with AIS in genetic model analysis.4. For LBX1, we found three SNPs associated with AIS:rs11190870, rsl322331 and rs625039. Among them rs1322331 owns the highest level of confidence.5. In dual luciferase system, GG genotype of rs1322331 can increase the expression of downstream gene while TT genotype have no significant influence.Conclusion1. Among the reported SNPs, rs11190870, rsl2885713, rs2300500, rs6570507 and rs4753426 are associated with AIS in Northern Chinese Han population.2. The most confidential SNP site in LBX1 which is associated with AIS is rs1322331.3. GG type of rs1322331 can increase the promoter’s function and facilitate downstream gene’s expression. So we hypothesis that overexpression of LBX1 leads to AIS.