中国汉族人群PAX1基因多态性与先天性脊柱侧凸遗传易感性的关联研究

目的 通过候选基因PAX1上单核苷酸多态性(SNP)位点的筛查,探索PAX1与中国汉族人群先天性脊柱测凸(CS)及其不同临床表型之间的关联.方法 采用病例-对照研究,127例中国汉族CS患者;127例对照为性别、年龄、民族与病例相匹配的非脊柱侧凸患者.用QIAamp DNABlood Mini Kit法提取外周血样本的全基因组DNA,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 4.0软件选取PAX1的标签SNPs.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SNPstreamUHT Genotyping系统对所选SNP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 4.0软件分析对照组SNP位点间是否存在连锁不平衡.结果 共筛选SNP1(rs17861031)和SNP2(rs6047590)两个位点,其基因型分布在病例和对照组中均符合Hardy-Weinberg平衡.两位点间不存在连锁不平衡.病例/对照组中等位基因频率分别为:SNP1A=37(15%)/37(15%)、SNP1G=217(85%)/217(85%),SNP2A=28(11%)/25(10%)、SNP2T=226(89%)/229(90%);基因型频率分别为:SNP1AA=2(2%)/2(2%)、SNP1AG=33(26%)/33(26%)、SNP1GG=92(72%)/92(72%),SNP2AA=2(2%)/2(2%)、SNP2AT=24(19%)/21(17)、SNP2TT=101(80%)/104(82%),差异均无统计学意义(P>0.05).在进一步与CS临床表型的关联分析中没有发现阳性位点.结论 在中国汉族人群中,PAX1基因可能不是引起CS及其不同临床表型的主要因素.

Association of PAX1 gene polymorphisms with susceptibility to congenital scoliosis in Chinese Han population

Objective To investigate the association of polymorphisms of PAX1 gene with congenital scoliosis (CS) in Chinese Han population and the relationship between the PAX1 gene polymorphisms and the clinical phenotypes of CS. Methods Peripheral blood samples were collected from 127 CS patients, 55 male and 72 female, aged (12.9 ±4.3) (2 - 23), and 127 sex- and age-matched controls. Based on genotype data from the International HapMap project, the tagging single nucleotide polymorphisms (tSNPs) were selected using Haploview 4.0 software. Hardy-Weinberg equilibrium was analyzed both in the control and case groups. The ease group was classified into different clinical phenotypes according to vertebral defect type, location of deformity, extent of developmental disruption, combined rib malformations, and neural canal deformity. Genotying of all selected SNPs was done by SNPstream technology. The association between phenotypes and SNP was analyzed. Pairwise linkage disequilibrium was calculated in the control population using Haploview 4.0 software. Results The sites: SNP1 (rs17861031) and SNP2(rs6047590), of PAX1 gene were genotyped and beth polymorphisms were distributed in line with the Hardy-Weinberg equilibrium in these 2 groups. There was no linkage disequilibrium between these 2 SNPs. The genotype frequencies of SNP1AA, SNP1AG, SNP1GG, SNP2AA, SNP2AT, and SNP2TT of the case group were 2%, 26%, 72%, 2%, 19%, and 80% respectively, all not significantly different from those of the control group (2%, 26%, 72%, 2%, 26%, and 82% respectively, all P >0.05). The allele frequencies of SNP1A, SNP1G, SNP2A, and SNP2T of the case group were 15%, 85%, 11%, and 89% respectively, all not significantly different from those of the control group (15%, 85%, 10%, and 90% respectively, all P > 0.05). No positive sites were found in different clinical penotypes. Conclusion The genetic variants of PAX1 gene may not be associated with the susceptibility to CS and different clinical phenotypes of CS in Chinese Han population.