中国汉族人群Trp2等位基因多态性与椎间盘退变性疾病的关联分析  

Association study of Trp2 allele polymorphism with degenerative disc disease in a Chinese Han nationality

作　　者：宋海峰[1] 吴志宏[2] 费琦[2] 闫家智[2] 刘正[2] 仉建国[2] 李书纲[2] 邱贵兴[2] 

机构地区：[1]天津市人民医院脊柱外科,300121 [2]中国医学科学院中国协和医科大学北京协和医院骨科

出　　处：《中华医学杂志》2010年第3期148-152,共5页National Medical Journal of China

基　　金：基金项目：国家自然科学基金（30672137,30772191）;中国博士后科学基金（20060400567）

摘　　要：目的探索Trp2等位基因多态性与中国汉族人群椎间盘退变性疾病（DDD）的关联。方法采用“病例-对照”研究方法，对Trp2等位基因对应的的单核苷酸多态性（SNP）位点进行筛查。125例中国汉族DDD患者（DDD^＋）与125例中国汉族非DDD受访者（DDD^-），其年龄、性别相匹配。提取外周血DNA，根据COL9A2基因在326位的氨基酸位置处存在两个突变位点，在NCBI基因序列数据库中确定其对应的位点SNPl（rs7533552）和SNP2（rs2077871）。根据椎间盘退变程度、单节段或多节段退变、退变的节段分布，将DDD^＋组为不同的亚型。用SNP分型系统-SNPstream UTT对所有样本的所选SNP位点行基因型鉴定。对检测数据分别行拟和优度r检验、基于等位基因频率／基因型的关联分析。结果病例组中和对照组中，两个位点的基因型分布均符合Hardy—Weinberg平衡；病例／对照组中等位基因频率分别为：SNP1A=105（42％）／117（58％）、SNP1G=145（47％）／133（53％），SNP2C=220（88％）／30（12％）、SNP2T=224（90％）／26（10％）；基因型频率分别为：SNP1AA=21（17％）／25（20％）、SNP1AG=63（50％）／67（54％），SNP1GG：41（33％）／33（36％）；SNP2CC=95（76％）／100（80％）、SNP2CT=30（24％）／24（19％），SNP2GG=1（0％）／1（％1），差异均无统计学意义。进一步对候选基因与DDD^＋组的不同亚型进行关联分析中，发现SNP2的基因型与椎间盘退变程度有相关性（χ^2=6．920，P=0．031）。结论中国汉族人群中，Trp2等位基因的基因多态性可能是决定椎间盘退变发展与退变程度的危险因素之一。Objective To investigate the association between Trp2 allele polymorphism with degenerative disc disease （DDD） in a Chinese Han population. Methods A total of 125 DDD patients （58 males and 67 females, 51.8 ±7. 6 years old）, and 125 controls matched in sex and age （63 males and 62 females, 45.3 ± 8. 3 years old） were recruited in the case-control study. Their peripheral blood samples were collected for DNA isolation. Based on NCBI genebank, the corresponding single nucleotide polymorphisms （ snp ） -SNP1 （ rs7533552 ） and SNP2 （ rs2077871 ） were identified. Hardy-Weinberg equilibrium was analyzed both in case and control groups. Then the case group was classified into different clinical phenotypes according to severity of degeneration, sole or multi-disc degeneration and different affected discs. Genotying of all selected SNPs was performed by SNP stream technology. The association analysis between phenotypes and SNPs was conducted. Pairwise linkage disequilibrium was calculated in control population using Haploview 4. 0 software. Results SNP1 （rs7533552） , SNP2 （ rs2077871 ） and corresponding SNP of Trp2 allele were gentyped and both polymorphisms distributed in line with Hardy- Weinberg equilibrium in case and control groups. Alleleic frequency of SNP1A, SNPIG, SNP2C and SNP2T （42% , 47% , 88% and 90% respectively） of case group were not significantly different from those of control group （48%, 53%, 88% and 10% respectively, all P 〉 0. 05 ）. Genotypic frequencies of SNP1AA, SNP1AG, SNP1GG, SNP2CC, SNP2CT and SNP23T in ease group were not significantly different from those of control group （ all P 〉 0. 05）. However there was an association with genotypic frequencies of SNP2 and severity of disc degeneration （χ^2 = 6. 920, P = 0. 031 ）. Conclusion Trp2 allele is one of risk faetors for the development and severity of DDD in a Chinese Han population.

关 键 词：椎间盘 多态性 单核苷酸 退变 

分 类 号：R681.53[医药卫生—骨科学] R739.63[医药卫生—外科学]