Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis
T F Rech1, S B C Moraes2, M Bredemeier3
1Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, Canoas, RS, Brasil.
Genetics and Molecular Research : GMR
|December 22, 2016
Summary
Matrix metalloproteinase (MMP) gene polymorphisms do not increase systemic sclerosis (SSc) risk. However, MMP1 and MMP3 variants are linked to specific SSc symptoms and laboratory findings, offering insights into disease characteristics.
Area of Science:
- Genetics
- Rheumatology
- Molecular Biology
Background:
- Systemic sclerosis (SSc) is characterized by fibrosis due to altered tissue architecture and extracellular matrix (ECM) deposition.
- Matrix metalloproteinases (MMPs) regulate ECM degradation, and their gene polymorphisms may affect ECM balance.
- Investigating MMP gene promoter polymorphisms can elucidate their role in SSc pathogenesis and clinical manifestations.
Purpose of the Study:
- To analyze the association of MMP1, MMP3, and MMP9 gene polymorphisms with susceptibility to systemic sclerosis (SSc).
- To investigate the relationship between these MMP polymorphisms and specific clinical and laboratory features of SSc.
Main Methods:
- Genotyping of MMP1 (-1607 1G/2G), MMP3 (-1171 5A/6A), and MMP9 (-1562 C/T) polymorphisms using polymerase chain reaction and restriction digestion.
- Comparison of genotype and allele frequencies between 98 SSc patients and 100 healthy controls of European descent.
- Secondary analysis correlating MMP genotypes with SSc clinical features (antinuclear autoantibodies, interstitial lung disease, calcinosis) and laboratory markers (anti-topoisomerase I antibodies, diffusing capacity for carbon monoxide).
Main Results:
- No significant differences in MMP genotype or allele frequencies were found between SSc patients and controls, indicating no association with SSc susceptibility.
- MMP1 1G/2G genotype was more frequent in patients with antinuclear autoantibodies (P=0.007).
- MMP1 1G/1G genotype was linked to interstitial lung disease (P=0.018).
- MMP3 6A/6A genotype was absent in patients with calcinosis (P=0.011).
- MMP3 5A/5A genotype correlated with anti-topoisomerase I antibodies (P=0.009) and reduced diffusing capacity for carbon monoxide (P=0.024).
Conclusions:
- MMP gene polymorphisms are not associated with the overall susceptibility to systemic sclerosis.
- Specific variants in MMP1 and MMP3 genes are associated with distinct clinical and laboratory features of SSc, suggesting a role in disease phenotype.
- These findings highlight potential genetic markers for specific SSc manifestations, warranting further investigation.
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