PMID- 12124858
OWN - NLM
STAT- MEDLINE
DCOM- 20020805
LR  - 20161124
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 46
IP  - 7
DP  - 2002 Jul
TI  - Stromelysin 1 (matrix metalloproteinase 3) and HLA-DRB1 gene polymorphisms: 
      Association with severity and progression of rheumatoid arthritis in a 
      prospective study.
PG  - 1754-62
AB  - OBJECTIVE: To test the hypothesis of an association between a polymorphism in the 
      matrix metalloproteinase 3 (MMP-3) gene promoter and the susceptibility, 
      severity, and progression of rheumatoid arthritis (RA), and to further document 
      the association between HLA-DRB1 alleles encoding the shared epitope (SE) and the 
      severity and progression of RA. METHODS: Patients with early RA (n = 103) were 
      included in this prospective study. A total radiographic damage score (TDS; by 
      the Sharp/van der Heijde method) was used to quantify RA severity at baseline and 
      after 4 years of followup. The 5A/6A biallelic polymorphism in the MMP-3 gene 
      promoter was analyzed using fluorescence-based polymerase chain reaction (PCR). 
      HLA-DRB1 genotyping was performed using PCR methods. Control subjects (n = 127) 
      were unrelated healthy individuals. RESULTS: MMP-3 allele carriage rates and 
      allele and genotype frequencies did not differ between patients and controls. The 
      MMP-3 6A/6A genotype was associated with the highest TDS both at baseline and 
      after a 4-year followup and with the highest progression of the TDS over the 4 
      years of followup. The DRB1 SE+/+ genotype was associated with the highest TDS 
      after a 4-year followup and with the highest progression of the TDS over the 4 
      years of followup. Patients homozygous for MMP-3 6A and DRB1 SE had the highest 
      progression of the TDS. CONCLUSION: This study provides the first evidence of an 
      association between a polymorphism in the MMP-3 gene promoter and the severity 
      and progression of RA, but not RA susceptibility. Investigation of this 
      polymorphism could be combined with that of DRB1 gene polymorphism to improve the 
      predictive accuracy and management strategy in early RA.
FAU - Constantin, Arnaud
AU  - Constantin A
AD  - Centre Hospitalier Universitaire Rangueil, INSERM U558, and INSERM U395, 
      Toulouse, France.
FAU - Lauwers-Cances, Valerie
AU  - Lauwers-Cances V
FAU - Navaux, Frederique
AU  - Navaux F
FAU - Abbal, Michel
AU  - Abbal M
FAU - van Meerwijk, Joost
AU  - van Meerwijk J
FAU - Mazieres, Bernard
AU  - Mazieres B
FAU - Cambon-Thomsen, Anne
AU  - Cambon-Thomsen A
FAU - Cantagrel, Alain
AU  - Cantagrel A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
CIN - Arthritis Rheum. 2003 Sep;48(9):2695-6. PMID: 13130493
MH  - Alleles
MH  - Arthritis, Rheumatoid/diagnostic imaging/*genetics
MH  - Disease Progression
MH  - Disease Susceptibility
MH  - Female
MH  - Follow-Up Studies
MH  - Genotype
MH  - HLA-DR Antigens/*genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 3/blood/*genetics
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Genetic
MH  - Promoter Regions, Genetic
MH  - Prospective Studies
MH  - Radiography
EDAT- 2002/07/19 10:00
MHDA- 2002/08/06 10:01
CRDT- 2002/07/19 10:00
PHST- 2002/07/19 10:00 [pubmed]
PHST- 2002/08/06 10:01 [medline]
PHST- 2002/07/19 10:00 [entrez]
AID - 10.1002/art.10336 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2002 Jul;46(7):1754-62. doi: 10.1002/art.10336.