基质金属蛋白酶9基因多态性与汉族女性青少年特发性脊柱侧凸的关联分析

摘要

目的 探讨基质金属蛋白酶9 (matrix metalloproteinase 9,MMP9)基因多态性与汉族女性青少年特发性脊柱侧凸(adolescent idiopathic scoliosis,AIS)发生和发展的关系.方法 以rs17576、rs2250889、rs1805088 3个标签单核苷酸多态性(single nucleotide polymorphisms,SNPs)作为遗传标记,通过TaqMan荧光探针法对190例AIS患者和190名年龄匹配汉族女性正常对照进行等位基因分型.对结果进行Hardy-Weinberg遗传平衡检验、Pearson x2检验、非条件Logistic回归分析、连锁不平衡检验和单倍型分析,并分析基因型与表型的关系.结果 正常对照组rs17576、rs2250889、rs1805088 3个位点基因型分布符合Hardy-Weinberg平衡(P＞0.05)；基因型-表型分析发现rs2250889位点基因型为CC的患者的最大Cobb角(48.50°)大于基因型为GG(25.98°)或GC(28.35°)者(P＜0.05),其侧凸程度较严重.结论 目前尚不能认为MMP9基因是汉族女性AIS的易感基因,但rs2250889纯合变异者脊柱侧凸较严重,提示MMP9异常可导致脊柱侧凸的进展.%Objective To determine whether the matrix metalloproteinase 9 gene (MMP9) polymorphism is associated with the onset or progression of adolescent idiopathic scoliosis (AIS) in Chinese Han female.Methods Three single nucleotide polymorphisms (SNPs) (rs17576,rs2250889,rs1805088) were genotyped through TaqMan-based real-time PCR assay in 190 AIS patients and 190 controls,all of whom were females from Chinese Han population with matched age.Analyses performed included Hardy-Weinberg equilibrium test,Pearson x2 test,Logistic regression analysis,linkage disequilibrium analysis and haplotype analysis.The mean maximum Cobb angles with different genotypes in case-only dataset were also compared.Results All 3 SNPs have reached Hardy-Weinberg equilibrium in the controls.Genotype and allele frequencies of all SNPs were found similar between cases and controls by Pearson x2 test and Logistic regression.Genotype-phenotype analysis showed that patients with CC genotype in rs2250889 featured larger maximum Cobb angles.Conclusion MMP9 may not be a predisposition gene of AIS in Han female.However,homozygous mutation in rs2250889 can render scoliosis more severe,implying that MMP9 defect may result in deterioration of AIS.