DVL2基因多态性与中国汉族人群先天性脊柱侧凸遗传易感性的关联研究

背景：近20年来小鼠的分子胚胎学研究进展获得了大量关于脊椎发育的分子信息，用同线性分析法确立先天性脊柱侧凸的候选基因已成为可能。目的：通过候选基因DVL2上关键单核苷酸多态性位点的筛查，探索DVL2与中国汉族人群先天性脊柱侧凸及其不同临床表型之间的关联。方法：采用病例-对照研究，入选127例中国汉族先天性脊柱侧凸患者和127例对照组。根据国际人类基因组单体型图计划提供的基因型数据，应用Haploview 4.1软件选取DVL2的标签和功能单核苷酸多态性。根据椎体畸形特点、畸形部位、畸形受累程度、有无合并肋骨畸形和椎管内畸形将病例组进一步分为不同临床表型。对所有样本应用SNPstream UHT Genotyping系统对所选单核苷酸多态性位点进行基因型鉴定；进一步进行基于基因型/等位基因频率的关联分析，并用Haploview 4.1软件分析对照组单核苷酸多态性位点间是否存在连锁不平衡。结果与结论：共筛选5个位点：单核苷酸多态性1(rs2074222)、单核苷酸多态性2(rs222837)、单核苷酸多态性3(rs222835)、单核苷酸多态性4(rs10671352)和单核苷酸多态性5(rs222836)，其基因型分布在病例和对照组中均符合Hardy-Weinberg平衡；5个位点处于完全连锁不平衡状态；5个位点的基因型/等位基因/单倍体型与先天性脊柱侧凸的发生风险之间不存在相关性。在进一步与先天性脊柱侧凸临床表型的关联分析中没有发现阳性位点。提示在中国汉族人群中DVL2基因可能不是引起先天性脊柱侧凸及其不同临床表型的主要因素，有待于进一步深入研究。

Association of DVL2 gene polymorphisms with susceptibility to congenital scoliosis in a Chinese Han population

BACKGROUND:In recent 20 years, mouse molecular embryology research has achieved much molecular information regarding vertebrae development. It is possible to determine the candidate gene for congenital scoliosis (CS) using linear analysis.OBJECTIVE:To investigate the association of DVL2 polymorphisms with CS clinical phenotypes in a Chinese Han population by screening key single nucleotide polymorphism sites of candidate gene DVL2.METHODS:A case-control design was applied in this study. A total of 127 patients diagnosed with CS and 127 scoliosis-free control subjects were enrolled in this study. According to genotype data from International HapMap project, the key single nucleotide polymorphisms (SNPs) of DVL2 were initially selected using Haploview 4.1 software. The patient group was classified into different clinical phenotypes according to vertebral defect type, deformity location, defect degree, combined rib malformations and neural canal deformity. All selected SNPs were genotype identified using SNPstream UHT Genotyping system. An association analysis based on genotype/allele frequency was further performed. Pairwised linkage disequilibrium was evaluated in the control group using Haploview 4.1 software. RESULTS AND CONCLUSION:Five SNPs of DVL2 gene were genotyped: SNP1 (rs2074222), SNP2 (rs222837), SNP3 (rs222835), SNP4 (rs10671352) and SNP5 (rs222836), and all polymorphisms were in Hardy-Weinberg equilibrium both in control and in patient groups. Five SNPs were in linkage disequilibrium. No association (P > 0.05) was observed between SNP genotypes/allele polymorphisms/haploid and CS risk and clinical phenotypes. Results showed that genetic variants of DVL2 gene may not be associated with the susceptibility to CS and different clinical phenotypes of CS in a Chinese Han population.