Effect of matrix metalloproteinase-3 functional SNP on serum matrix metalloproteinase-3 level and outcome measures in Japanese RA patients.
OBJECTIVE
A bi-allelic polymorphism on the promoter region, -1612 ins/del A, was found to influence the production of MMP-3. Since MMP-3 plays a particularly pivotal role in joint destruction, the MMP-3 gene is thought to be an interesting target gene of disease severity in RA. We attempt to determine whether the MMP-3 promoter polymorphism is associated with serum titre of MMP-3, disease activity and severity in Japanese RA patients.


METHODS
DNA samples were obtained from 1504 RA patients as part of the Institute of Rheumatology Rheumatoid Arthritis observational cohort study. From the 2006 spring data, serum MMP-3 levels of 820 patients were available by enzyme immunoassay. Joint damage score at 5-yr disease duration could be measured using the Sharp/van der Heijde method in 162 patients. Genotyping of -1612 ins/del A was performed using fluorescent-labelled fragment analysis. Differences in serum MMP-3 level and joint damage score among genotypes of -1612 ins/del A polymorphism were analysed by linear regression analysis.


RESULTS
No significant differences were found among MMP-3 genotypes on patient characteristics including disease activity score (P = 0.51) or health assessment questionnaire (P = 0.99). A significant effect of risk allele on serum MMP-3 level was observed (P = 0.038), while no significant effect was observed on radiographic joint damage (P = 0.47).


CONCLUSIONS
We conclude that MMP-3 functional polymorphism is associated with serum MMP-3 titre, but is not a direct predictor for outcome measures in Japanese RA patients.
Tsukahara
S
S
Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada, Shinjuku, Tokyo 162-0054, Japan.
Shinozaki
M
M
Ikari
K
K
Mochizuki
T
T
Inoue
E
E
Tomatsu
T
T
Hara
M
M
Yamanaka
H
H
Kamatani
N
N
Momohara
S
S
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006304:Health Status; D006801:Humans; D007596:Joints / Q000473:pathology / Q000503:physiopathology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires
D019278:Matrix Metalloproteinase 3