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Collagenase-1 (MMP-1) and HLA-DRB1 Gene Polymorphisms in Rheumatoid Arthritis:
A Prospective Longitudinal Study
ARNAUD CONSTANTIN, VALÉRIE LAUWERS-CANCÈS, FRÉDÉRIQUE NAVAUX, MICHEL ABBAL, JOOST VAN MEERWIJK, BERNARD MAZIÈRES, ANNE CAMBON-THOMSEN, and ALAIN CANTAGREL
ABSTRACT. 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-DRB1 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. (J Rheumatol 2002;29:15-20) Key Indexing Terms:
COLLAGENASE-1 GENE |