基质金属蛋白酶3的基因多态性及其mRNA表达水平与类风湿关节炎的关系研究

Genetic polymorphism of matrix metallopoteiase-3 and correlation between its mRNA expression and rheumatoid arthritis

目的探讨基质金属蛋白酶-3(MMP-3)的基因多态性及其mRNA表达水平与类风湿关节炎(RA)骨侵蚀发生的关系。方法记录患者相关临床指标并计算Sharp评分。采用焦磷酸测序(pyrosequencing)方法检测所有样本MMP-3的基因型。实时定量PCR检测MMP-3的mRNA表达水平。结果 MMP-3在RA患者和对照组中基因频率分布比较差异无统计学意义(P>0.05)。患者组中具有6A/6A基因型的患者,其病程<6年时Sharp评分高于不具有纯合子6A基因型的患者(P<0.05)。RA患者MMP-3的mRNA表达水平高于健康对照组,活动期RA患者MMP-3的mRNA表达水平高于非活动期的患者。在RA患者中,具有6A/6A基因型的患者和不具有这种基因型的患者的MMP-3的mRNA表达水平无显著差异;具有6A/6A基因型的RA患者中,其病程≤6年和病程>6年时mRNA的表达水平无显著差异。结论 MMP-3基因多态性与中国华东地区汉族人群RA的易感性无关,与病程<6年RA患者关节的骨侵蚀严重程度相关。RA患者MMP-3的mRNA表达水平高于健康对照人群,活动期RA患者MMP-3的mRNA表达水平高于非活动期的患者。

Objective To explore the genetic polymorphism of matrix metallopoteiase- 3（MMP-3）and correlation between its mRNA expression and rheumatoid arthritis.Methods Clinical indexes of patients were recorded and Sharp score wasevaluated.Genotypes in all the samples of MMP-3 were detected by method of pyrosequencing, and the expression of mRNA of MMP-3 was detected by real-time PCR.Results There were no significant difference of gene frequency distribution of MMP-3 between two groups（P 0.05）. In RA group（course of disease≤ 6 years）,the Sharp score of patients with 6A polymorphism was significantly higher than patients without homozygote 6A polymorphism（P 0.05）. Expression of mRNA of MMP-3 in RA group was significantly higher than that in the control group（P 0.05）, and the expression of mRNA of MMP-3 in RA patients with active stage was significantly higher than that in RA patients without active stage（P 0.05）. In RA group, there was no significant difference of expression of mRNA of MMP-3between the patients with genotype of 6A/6A and the patients without genotype of 6A/6A. In the patients with genotype of 6A/6A, there was no significant difference of expression of mRNA between the patients with course of disease ≤ 6 years and the patients with course of disease 6years.Conclusion Genetic polymorphism of MMP-3 is not associated with susceptibility of RA in the Han people in eastern part of China,but is associated with degree of jointerosion（disease courses≤ 6 years）. Expression of mRNA of MMP-3 in RA patients was higher than that in the normalpeople, and the expression of mRNA of MMP-3 in RA patients with active stage was higher than that in RA patients without active stage.