易感基因CELSR2与汉族青少年特发性脊柱侧凸的相关性研究

The correlation between CELSR2 gene and the susceptibility of adolescent idiopathic scoliosis in the Chinese Han nationality

中文关键词:  青少年特发性脊柱侧凸  CELSR2  突变  基因多态性

英文关键词:Adolescent idiopathic scoliosis  CELSR2  Mutation  Single nucleotide polymorphism sites

中文摘要:

  【摘要】目的：在中国汉族人群中验证易感基因CELSR2与青少年特发性脊柱侧凸（adolescent idiopathic scoliosis，AIS）发病的相关性。方法：利用等位基因特异性多重连接酶检测反应在1794例AIS患者和1040例正常对照人群中对既往报道的CELSR2基因的易感位点rs141489111、rs6698843和rs2281894进行基因分型。同时在本中心全基因组数据库中分析CELSR2基因其他单核苷酸多态性位点（SNP）的基因分型信息。术中收集45例AIS患者（AIS组）和10例年龄匹配的脊柱外伤患者（对照组）的椎旁肌，比较两组椎旁肌中基因表达水平的差异。利用卡方检验分析组间SNP位点最小等位基因频率差异，采用T检验对组间的基因表达水平进行统计分析。结果：1794例AIS患者和1040例正常对照人群中，rs141489111位点未检测到突变，所有研究对象基因型均为GG。SNP位点rs6698843和rs2281894的基因型及等位基因频率在AIS和正常对照人群间未见显著性差异（P＜0.05）。GWAS数据库显示其他7个位于CELSR2基因上的SNP位点与AIS亦无显著相关性（P＜0.05）。CELSR2基因在AIS组和对照组椎旁肌的表达水平无显著性差异（P＜0.05）。结论：既往报道的易感基因CELSR2上的突变位点和多态性位点均未在中国汉族人群中得到验证，AIS患者椎旁肌组织中CELSR2表达未见明显异常。CELSR2可能与汉族AIS的发生无关。

英文摘要:

  【Abstract】 Objectives: To validate the correlation between the CELSR2 gene and the susceptibility of adolescent idiopathic scoliosis(AIS) in the Chinese Han population. Methods: Allelic specific multiple ligase detection reactions were used to genotype the previously reported CELSR2 gene susceptibility loci rs141489111, rs6698843 and rs2281894 in 1794 AIS patients and 1040 healthy 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(AIS group) and 10 age-matched spinal trauma patients(Control group) were collected during the operation, which were used to evaluate the expression tissue of CELSR2. Chi-square test was used to analyze the difference of the minor allele frequency(MAF) of SNPs between the two groups, and Student′s t test was used to statistically compare the gene expression level. Results: No mutation was detected in the rs141489111 locus of 1794 AIS patients or 1040 healthy controls, and all subjects had homozygous genotype GG. The genotypes and allele frequencies of rs6698843 and rs2281894 were not significantly different between the AIS and control groups(P＜0.05). The GWAS database showed that there was no significant correlation regarding genotypes or allele frequencies of the other seven SNP loci located in the CELSR2 gene between the two groups(P＜0.05). Moreover, CELSR2 mRNA expression of paraspinal muscle in AIS patients was comparable with that in the controls(P＜0.05). Conclusions: The mutation and polymorphisms sites of CELSR2 gene mentioned in previous reports have not been validated in Chinese Han population in our study, and there was no obvious abnormality in CELSR2 expression in paravertebral muscles of AIS patients. Therefore, CELSR2 may not be related to the onset of AIS in Han population.