Hunter Medical Research Institute, and University of Newcastle, Australia.
Mult Scler. 2014 Apr;20(4):489-91. doi: 10.1177/1352458513498127. Epub 2013 Jul 29.
Matrix metalloproteinase 9 (MMP9) is involved in multiple sclerosis (MS) aetiology. Previously, we identified differential gene expression of plasminogen activation cascade genes in MS patients. Based on our gene expression results, we wanted to identify whether polymorphisms in the genes associated with the plasminogen pathway could predict MS risk. We genotyped 1153 trio families, 727 MS cases and 604 healthy controls for 17 polymorphisms in MMP9, plasminogen activator urokinase (PLAU), PLAU receptor (PLAUR) and serpin peptidase inhibitor/clade 2/member B2 (SERPINB2) genes. No associations were found between the 17 polymorphisms and MS. Also, gene expression levels were analysed according to genotype: no associations were observed. In conclusion despite the consistent evidence for the role of MMP9 and the plasminogen activation cascade in MS, we found no associations between genotype nor gene expression. This suggested there are other potentially modifiable factors influencing gene expression in MS.
基质金属蛋白酶 9（MMP9）参与多发性硬化症（MS）的发病机制。此前，我们已经鉴定出 MS 患者纤溶酶原激活级联基因的差异表达。基于我们的基因表达结果，我们想确定与纤溶酶原途径相关的基因中的多态性是否可以预测 MS 风险。我们对 1153 个三核苷酸家族、727 例 MS 病例和 604 例健康对照者的基质金属蛋白酶 9（MMP9）、纤溶酶原激活物尿激酶（PLAU）、PLAU 受体（PLAUR）和丝氨酸蛋白酶抑制剂/ 2 族/成员 B2（SERPINB2）基因中的 17 个多态性进行了基因分型。未发现 17 个多态性与 MS 之间存在关联。此外，还根据基因型分析了基因表达水平：未观察到关联。总之，尽管 MMP9 和纤溶酶原激活级联在 MS 中的作用有一致的证据，但我们未发现基因型或基因表达之间存在关联。这表明在 MS 中存在其他可能影响基因表达的可调节因素。
