Collagenase-1 (MMP-1) and HLA-DRB1 gene polymorphisms in rheumatoid arthritis: a prospective longitudinal study.

Abstract

OBJECTIVE:

Rheumatoid arthritis (RA) is characterized by chronic synovitis leading to permanent damage of the joints. Collagenase-1 (MMP-1) is a matrix metalloproteinase involved in articular cartilage degradation. We investigated the association between a biallelic polymorphism in the MMP-1 gene promoter and the susceptibility to, and severity of, RA. We also investigated the association between HLA-DRB1 gene polymorphism and severity of RA.

METHODS:

One hundred and three patients with early RA were included in this prospective longitudinal study. A radiographic damage score was used to quantify disease severity at baseline and after 4 years of followup. MMP-1 polymorphism genotyping was analyzed using a fluorescent-based polymerase chain reaction (PCR). HLA-DRB1 genotypes were determined by PCR sequence-specific oligonucleotide probes. One hundred and thirty-three healthy individuals were used as controls.

RESULTS:

MMP-1 allele and genotype frequencies did not differ between RA patients and controls. The radiographic damage or its progression over the 4 years of followup did not differ across MMP-1 genotypes. The radiographic damage score and its progression over the 4 years of followup differed across HLA-DRB1 genotypes. The HLA-DRB I shared epitope +/+ genotype was associated with the highest radiographic damage score and the highest progression, while the shared epitope -/- genotype was associated with the lowest.

CONCLUSION:

Our results do not support the hypothesis of an association between this particular polymorphism in the MMP-1 gene promoter and susceptibility to, or severity of, RA. This study confirms the previous reports of an association between the HLA-DRB1 gene polymorphism and severity of RA.

• Authors: Arnaud Constantin, Valérie Lauwers-Cancès, Frédérique Navaux, Michel Abbal, Joost van Meerwijk, Bernard Mazières, Anne Cambon-Thomsen, Alain Cantagrel
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 29 Issue 1 Pg. 15-20 (Jan 2002) ISSN: 0315-162X [Print] Canada
• PMID: 11824952 (Publication Type: Journal Article)

Chemical References

• HLA-DR Antigens
• HLA-DRB1 Chains
• Collagenases
• collagenase 1

Topics

• Adult
• Aged
• Arthritis, Rheumatoid (enzymology, genetics, physiopathology)
• Cartilage, Articular (diagnostic imaging, enzymology, pathology)
• Collagenases (genetics)
• DNA Mutational Analysis
• Disease Progression
• Female
• Gene Frequency
• Genetic Predisposition to Disease (genetics)
• Genetic Testing
• Genotype
• HLA-DR Antigens (genetics)
• HLA-DRB1 Chains
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Mutation (genetics)
• Polymorphism, Genetic (genetics)
• Predictive Value of Tests
• Prospective Studies
• Radiography
• Time Factors