MS susceptibility is not affected by single nucleotide polymorphisms in the MMP9 gene
S Nischwitz1, C Wolf1, T F M Andlauer1
1Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany.
Journal of Neuroimmunology
|February 12, 2015
Summary
Genetic variants in matrix metalloproteinase 9 (MMP9) do not significantly impact multiple sclerosis (MS) susceptibility. A study found no genome-wide association, with a variant in WFDC2 showing the strongest link, not MMP9 itself.
Area of Science:
- Neuroimmunology
- Genetics
- Molecular Biology
Background:
- Matrix metalloproteinase 9 (MMP9) is implicated in the pathology of multiple sclerosis (MS).
- The role of genetic variations in MMP9 influencing MS susceptibility remains unclear and debated.
Purpose of the Study:
- To investigate the association between single nucleotide polymorphisms (SNPs) in and around the MMP9 gene and MS susceptibility.
- To clarify the contribution of MMP9 genetic variants to the development of multiple sclerosis.
Main Methods:
- SNP genotyping and imputation were performed for a region encompassing MMP9 and flanking areas (2Mbp upstream and downstream).
- Statistical analyses were conducted to assess the association between identified SNPs and MS.
- A meta-analysis combined the study's data with previously published findings.
Main Results:
- No MMP9 SNPs reached genome-wide significance for association with MS.
- The SNP rs6073751, located within the WFDC2 gene, showed the strongest association with MS.
- The SNP rs3918242, previously reported to be associated with MS, only reached nominal significance in this study.
- Meta-analysis did not confirm the association of rs3918242 with MS.
Conclusions:
- Genetic variations directly within the MMP9 gene region are unlikely to be major determinants of MS susceptibility.
- The strongest observed association was with a SNP in WFDC2, suggesting potential non-MMP9 genetic influences.
- Previous findings on MMP9 SNPs and MS require re-evaluation based on current comprehensive genetic analyses.
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