摘要
目的:探讨我国汉族人群HAIRY-AND-ENHANCER-OF-SPLIT-7(HES7)基凶多态性与先天性脊柱侧凸(congenital scoliosis,CS)的关联性。方法:2005年9月-2007年5月在我院住院治疗的性别与年龄完全匹配的CS患者和非发育性畸形疾病患者(对照组)各123例,均为汉族,从外周血中提取基因组DNA。从美国国立生物技术信息中心(NCBI)数据库选取HES7基因rs3027279和rs1442849两个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点,采用超高通量SNP分型系统对这两个位点进行基因分型,对检测的结果进行Hardy-Weinberg(H-W)平衡检验、卡方(X^2)检验、连锁不平衡(linkage disequilibrium,LD)分析、单位点非条件Logistic回归分析和多位点单倍型非条件Logistic回归分析,判断日ES7多态性与CS易感性是否存在关联性。结果:两个SNP位点都具有多态性,且均符合H-W平衡。rs3027279位点中,C和A两种等位基因的频率在对照组和CS组间的差异具有显著性(X^2=4.651,P〈0.05);C/C和C/A两种基因型在两组间的差异具有显著性(X^2=5.857,P〈0.05)。rs1442849位点中,A和G两种等位基因在两组间的差异具有显著性(X^2=7.963,P〈0.05);G/G、G/A和A/A三种基因型在两组间的差异有统计学意义(X^2=7.919,P〈0.05)。非条件Logistic回归分析表明rs1442849位点的A/A基因型对CS可能具有保护作用(P=0.018〈0.05,OR=0.35,95%CI=0.17-0.74),而rs3027279位点的C/A基因型可能会增加CS的发病风险(P=0.015〈0.05,OR=1.93,95%CI=1.13-3.30)。LD分析示该两位点存在连锁不平衡关系(D′=0.923,r^2=0.3812),单倍型非条件Logistic回归分析表明单倍型Hap3-GA可能会增加CS的发病风险(P=0.008〈0.01,OR=2.14,95%CI=1.23-3.74)。结论:中国汉族人群HES7的rs3027279和rs1442849两个位点存在多态性,该两个位点的多态性可能与CS的易感性有一定关联性。
Objective:To explore the association between genetic polymorphisms of HAIRY-AND-EN- HANCER-OF-SPLIT-7(HES7) and congenital scoliosis (CS) in Han population.Method:246 cases of congenital scoliosis and noncongenital controls in our hospital were collected repectively,in which the age and sex were fully matched.All paticipants were Chinese Han population.The genome DNA was extracted from peripheral blood sample.Two SNPs were defined for HES7 using NCBI database.The genotypes of two SNPs were determined by SNPstream UHT Genotyping System.Statistical analysis,including Hardy-Wcinberg equilibrium test,Pearson chi-square test,linkage disequilibrium analysis ,single SNP unconditional Logistic regression analysis and multiple SNPs unconditional Logistic regression analysis,were performed to determine the association between the polymorphisms of HES7 and the susceptibility of nonsyndromal CS.Result:Polymorphisms were found in both SNPs and in accordance with Hardy-Weinberg equilibrium.For SNP rs3027279,the difference of two alleles (C and A) frequencies between CS and control groups was statistically significant(X^2=4.651 ,P〈 0.05).Analysis also showed the difference of two genotypes(C/C and C/A) frequencies between two groups was signifieant(X^2=5.857,P〈0.05).For SNP rs1442849,both difference of two alleles(A and G) frequencies and dif- ference of three genotypes(G/G,G/A and AA) frequencies between two groups were shown statistically significant(X^2=7.963,P〈0.05; X^2=7.919,P〈0.05;respectively).The unconditional Logistic regression analysis showed A/A genotype of SNP rs1442849 may be a protective factor (P=0.018〈0.05,0R=0.35,95%CI=0.17-0.74) for the onset of CS,while C/A genotype of SNP rs3027279 increased the onset risk (P=0.015〈0.05,0R=1.93,95% CI=1.13-3.30) of CS.Linkage disequilibrium analysis demonstrated the existence of linkage disequilibrium between the two SNPs.The haplotype unconditional Logistic regression analysis showed Hap3-GA may increase the onset risk (P=0.008〈0.01,OR=2.14,95%CI=l.23-3.74) of CS. Conclusion:The genetic polymorphisms in rs1442849 and rs3027279 of HES7 exist in Chinese Hun population.The polymorphisms of these two SNPs may be associated with the susceptibility of congenital scoliosis.
出处
《中国脊柱脊髓杂志》
CAS
CSCD
北大核心
2009年第3期222-226,共5页
Chinese Journal of Spine and Spinal Cord
关键词
先天性脊柱侧凸
单核苷酸多态性
HES7
关联分析
Congenital scoliosis
Single nucleotide polymorphisms
Hairy-and-enhancer-of-split-7
Associationanalysis