RT Journal Article
T1 Regulatory polymorphisms in extracellular matrix protease genes and susceptibility to rheumatoid arthritis: a case-control study
A1 Rodríguez López, Julio
A1 Pérez Pampín, Eva
A1 Gómez-Reino Carnota, Juan Jesús
A1 González Martínez-Pedrayo, Antonio
K1 Rheumatoid Arthritis
K1 Rheumatoid Arthritis Patient
K1 Human Leukocyte Antigen
K1 Rheumatoid Arthritis Susceptibility
K1 Human Leukocyte Antigen Molecule
AB Many extracellular matrix (ECM) proteases seem to be important in rheumatoid arthritis (RA) and regulation of their transcription levels is a critical mechanism for controlling their activity. We have investigated, therefore, whether the best-characterized single nucleotide polymorphisms (SNPs) affecting transcription of the ECM proteases that have been related with joint pathology are associated with RA susceptibility. Nine SNPs in eight genes were selected by bibliographic search, including SNPs in the genes encoding matrix metalloproteinase (MMP)1, MMP2, MMP3, MMP7, MMP9, MMP13, plasminogen activator, tissue type (PLAT) and PAI-1. They were studied in a case-control setting that included 550 RA patients and 652 controls of Spanish ancestry from a single center. Genotyping was performed by single-base extension. Only two of the nine SNPs showed significant association with RA susceptibility. RA patients showed increased frequencies of the -7351 T allele of the gene encoding PLAT (36.4% versus 32.1% in controls, p = 0.026) and the -1306 T allele of the gene encoding MMP2 (24.5% versus 20.3% in controls, p = 0.013). These two alleles seemed to cooperate according to an additive model with respect to increased RA susceptibility (p = 0.004), and they were the low-expression alleles of the respective SNPs in a PLAT enhancer and the MMP2 promoter. These findings are in agreement with previous data suggesting that these two ECM proteases have a protective role in RA pathology. Confirmation of these associations will be needed to support these hypotheses. The remaining SNPs did not show association, either individually or collectively. Therefore, although regulatory SNPs in ECM proteases did not show any major effect on RA susceptibility, it was possible to find modest associations that, if replicated, will have interesting implications in the understanding of RA pathology
PB BMC
SN 1478-6354
YR 2005
FD 2005
LK http://hdl.handle.net/10347/22954
UL http://hdl.handle.net/10347/22954
LA eng
NO Rodriguez-Lopez, J., Perez-Pampin, E., Gomez-Reino, J.J. et al. Regulatory polymorphisms in extracellular matrix protease genes and susceptibility to rheumatoid arthritis: a case-control study. Arthritis Res Ther 8, R1 (2005). https://doi.org/10.1186/ar1849
NO This project was supported by grant PI02/0713 from the Instituto de Salud Carlos III (Spain) with participation of funds from FEDER (European Union). JR-L is the recipient of a scholarship of the National Program for the Training of University Professors of the Spanish Ministry of Education. AG was supported by the Instituto de Salud Carlos III (Spain)
DS Minerva
RD 24 abr 2026