Variation in the matrix metalloproteinase-3, -7, -12 and -13 genes is associated with functional status in rheumatoid arthritis

Abstract

As matrix metalloproteinases (MMPs) play an important role in rheumatoid arthritis, we investigated whether variation in MMP genes was associated with functional disability in rheumatoid arthritis patients. A cohort of patients with seropositive rheumatoid arthritis were recruited and genotyped for the MMP1-1607 1G > 2G, MMP3-1612 5A > 6A, MMP7-153C > T, MMP7-181G > A, MMP12-82A > G and MMP13-77A > G polymorphisms. Genotypes were then analysed in relation to functional disability assessed by Steinbrocker index and Health Assessment Questionnaire (HAQ) score. We detected an association between the MMP13-77 A > G polymorphism and Steinbrocker index, with patients of the A/A genotype having higher score than patients of the A/G or G/G genotype (P = 0.005), and the association remained significant after adjusting for age, sex, erythrocyte sedimentation rate, presence of erosive disease, Ritchie score, prednisolone therapy and years of diagnosis (P = 0.003). We also observed a relationship of Steinbrocker index with the MMP3-1612 5A > 6A, MMP7-181 A > G and MMP12-82A > G polymorphisms (P = 0.082, P = 0.037 and P = 0.045). No association was detected between the MMP1-1607 1G > 2G and MMP7-153C > T polymorphisms and either Steinbrocker index or HAQ score. These results suggest that MMP3, MMP7, MMP12 and MMP13 genotypes may play a role in determining functional status of rheumatoid arthritis.