Lack of association of a functionally relevant single nucleotide polymorphism of matrix metalloproteinase-1 promoter
R W Johnson1, J D Reveille, T McNearney
1Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, The University of Texas-Houston Medical School, Houston, TX 77030, USA.
Abstract:
Matrix metalloproteinase 1 (MMP-1) is necessary for degradation of interstitial collagen types I, II, and III, which are the major constituents of the extracellular matrix (ECM). Increased expression of MMP-1 has been correlated with invasiveness of certain malignancies and cartilage degradation in rheumatoid arthritis. Increased transcriptional activity of MMP-1 has been reported with a single nucleotide polymorphism (SNP) of the MMP-1 promoter. Systemic sclerosis (SSc) is characterized by increased accumulation and turnover of collagen and other components of ECM. Previous studies have reported increased expression of MMP-1 transcripts in SSc fibroblasts. Therefore, we sought to determine if SSc patients with early disease (< or =5 years) from a multi-ethnic cohort were more or less likely than ethnically-matched normal controls to have an increased frequency of the high promoter activity MMP-1 genotype and whether MMP-1 promoter genotypes correlated with any of the major clinical manifestations of SSc. The results show that the frequency of the high activity promoter genotype in either the heterozygous or homozygous state did not differ significantly between SSc patients and ethnically-matched controls, or between SSc patients with either diffuse or limited scleroderma. Furthermore, MMP-1 promoter genotypes did not significantly correlate with any of the major clinical manifestations of SSc.
Insights
The study found no significant difference in matrix metalloproteinase 1 (MMP-1) high promoter activity genotypes between systemic sclerosis (SSc) patients and controls. MMP-1 genotypes did not correlate with SSc clinical features.
Area of Science:
- Genetics
- Rheumatology
- Biochemistry
Background:
- Matrix metalloproteinase 1 (MMP-1) degrades extracellular matrix (ECM) collagen.
- Elevated MMP-1 expression is linked to cancer invasiveness and rheumatoid arthritis.
- Previous research indicated increased MMP-1 transcripts in systemic sclerosis (SSc) fibroblasts.
Purpose of the Study:
- To investigate the frequency of high promoter activity MMP-1 genotypes in early SSc patients from a multi-ethnic cohort.
- To determine if these genotypes correlate with clinical manifestations of SSc.
Main Methods:
- Genotyping of MMP-1 promoter single nucleotide polymorphism (SNP) in SSc patients and ethnically-matched controls.
- Analysis of genotype distribution in relation to SSc subtypes (diffuse vs. limited).
- Correlation analysis between MMP-1 genotypes and major SSc clinical features.
Main Results:
- The frequency of the high activity MMP-1 promoter genotype (heterozygous or homozygous) did not significantly differ between SSc patients and controls.
- No significant difference in genotype frequency was observed between diffuse and limited SSc subtypes.
- MMP-1 promoter genotypes showed no significant correlation with major SSc clinical manifestations.
Conclusions:
- The high promoter activity MMP-1 genotype is not a significant risk factor for developing early systemic sclerosis.
- MMP-1 promoter genotype does not appear to influence the clinical presentation of SSc.
