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


CONCLUSIONS
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.
Constantin
Arnaud
A
Department of Rheumatology and Immunology, CHU Rangueil, France.
Lauwers-Cancès
Valérie
V
Navaux
Frédérique
F
Abbal
Michel
M
van Meerwijk
Joost
J
Mazières
Bernard
B
Cambon-Thomsen
Anne
A
Cantagrel
Alain
A
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000473:pathology; D017364:Collagenases / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011859:Radiography; D013997:Time Factors
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D017364:Collagenases; C417249:collagenase 1