title: Common genetic variants in the plasminogen activation pathway are not associated with multiple sclerosis.
abstract: 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.
authors.affiliation: Hunter Medical Research Institute, and University of Newcastle, Australia.
authors.forename: Mathew B
authors.initials: MB
authors.lastname: Cox
authors.forename: Nikola A
authors.initials: NA
authors.lastname: Bowden
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Scott
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D010958:Plasminogen / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics*; D015843:Serpins / Q000235:genetics*; D059467:Transcriptome; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
chemical_list: D055293:Receptors, Urokinase Plasminogen Activator; D015843:Serpins; C434683:serpin-2; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Gene expression; genotype; matrix metalloproteinase 9; multiple sclerosis; plasminogen; plasminogen activation pathway; plasminogen activator urokinase; polymorphism; serpin peptidase inhibitor