中国汉族人群WNT3A基因多态性与先天性脊柱侧凸遗传易感性的关系

Association study of WNT3A gene polymorphisms with the susceptibility to congenital scoliosis in a Chinese Han population

目的 探索WNT3A基因与中国汉族人群先天性脊柱侧凸（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;所有病例对照为性别、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,选取WNT3A的主要功能性单核苷酸多态性（SNP）.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 4.1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（rs964941）和SNP2（rs752107）2个位点,病例/对照组中等位基因频率分别为：SNP1C=127（50%）/115（45%）、SNP1t=127（50%）/139（55%）,SNP2C=197（78%）/200（79%）、SNP2t=57（22%）/54（21%）;基因型频率分别为：SNP1CC=35（28%）/25（20%）、SNP1Ct=57（45%）/65（51%）,SNP1Tt=35（28%）/37（29%）,SNP2CC=73（57%）/81（64%）、SNP2Ct=51（40%）/38（30%）、SNP2Tt=3（2%）/8（6%）,差异均无统计学意义（P＞0.05）.SNP1和SNP2间不存在连锁不平衡.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,WNT3A基因遗传变异可能不是引起CS及其不同临床表型的主要因素.

Objective To investigate whether the polymorphisms of WNT3A gene are associated with congenital scoliosis （CS） and its various clinical phenotypes in a Chinese Han population.Methods A total of 127 CS patients admitted into PUMC were enrolled into this case-control study between October 2005 and September 2007.There were 55 boys and 72 girls with a mean age of 12.90 years old.Another 127 scoliosis-free control subjects at the same hospital during the same study period were frequency-matched with regards to age （＋3 years） and gender.Genomic DNA was extracted by QIAamp DNA Blood Mini Kit from peripheral blood leukocytes of each subject who had signed informed consent.Based on the genotypic data from the International HapMap project,the main functional single nucleotide polymorphisms （SNPs） were initially selected.The patients in the case group were classified into different clinical phenotypes according to vertebral defect type,location of deformity,extent of developmental disruption,combined rib malformations and neural canal deformity.The genotying of all selected SNPs was performed by SNPstream technology （Beckman Coulter SNPstream）.All data of SNPs with polymorphism were processed by the association analysis based on a single SNP and between phenotypes and SNPs.And the pairwise linkage disequilibrium was calculated in the control population by Haploview 4.1 software.Results The SNP1 （rs964941） and SNP2（rs752107） of WNT3A were genotyped.There was no linkage disequilibrium between two SNPs.No association was observed between SNP1 and SNP2 genotypes or allele polymorphisms and risk of CS and various clinical phenotypes （P ＞ 0.05）.Conclusions The genetic variants of WNT3A gene may not be associated with the susceptibility to CS and various clinical phenotypes of CS in Chinese Han population.