基质金属蛋白酶-3基因多态性与儿童大骨节病关联分析

摘要

Objective To investigate the role of matrix metalloproteinases-3 (MMP-3) gene in the pathogenesis and progression of kashin-beck disease (KBD) in children.Methods Serum of 35 KBD cases (case group) and 84 healthy children (control group) was collected and genomic DNA was obtained.Eight SNPs in MMP-3 genotypes were grouped using Sequenom assARRAY RS1000.The frequencies of alleles and genotypes were compared between two groups.Three genetic models ( dominant, recessive and additive) were evaluated using unconditional Logistic regression analysis.Results The allele frequency of rs679620 was significantly different between two groups (χ2 =4.18,P<0.05) .Two SNPs loci of rs679620 and rs591058 were found to be significantly associated with KBD in children (χ2 value was 9.43 and 6.65, respectively, both P<0.05).And the genotype T/T in rs679620 and T/T in rs591058 showed an association with an increased risk of KBD in the recessive model [OR (95% CI) was 5.05 (1.98-12.91) and 3.68 (1.40-9.67), respectively]. Conclusion MMP-3 plays an important role in the pathogenesis and progression of KBD in children.The genotypes T/T in rs679620 and T/T in rs591058 are significantly associated with high risk of KBD in children.%目的：探讨基质金属蛋白酶-3（MMP-3）基因多态性在儿童大骨节病（KBD）发病中的作用。方法收集35例KBD患儿（病例组）和84例健康儿童（对照组）全血并提取全血基因组DNA，应用Sequenom assARRAY RS1000分型技术对MMP-3上8个单核苷酸多态性（SNP）位点进行基因分型，比较病例组与对照组等位基因和基因型的分布差异，用非条件Logistics回归模型衡量各等位基因在3种遗传模型（显性、隐形和加和模型）下的效益。结果 rs679620等位基因在两组儿童中分布有显著性差异（χ2＝4．18，P＜0．05），2个SNP位点rs679620、rs591058与KBD显著相关（χ2值分别为9．43和6．65，均P＜0．05）。在隐性遗传模式下，rs679620基因型T/T和rs591058基因型T/T与儿童KBD的高风险相关联，OR（95％CI）分别为5．05（1．98～12．91）、3．68（1．40～9．67）。结论 MMP-3在儿童KBD发病中起重要作用，rs679620基因型T/T和rs591058基因型T/T与儿童KBD易感性有关。