PT - JOURNAL ARTICLE AU - Mirko Manetti AU - Lidia Ibba-Manneschi AU - Cinzia Fatini AU - Serena Guiducci AU - Giovanna Cuomo AU - Claudia Bonino AU - Laura Bazzichi AU - Vasiliki Liakouli AU - Roberto Giacomelli AU - Rosanna Abbate AU - Stefano Bombardieri AU - Carlomaurizio Montecucco AU - Gabriele Valentini AU - Marco Matucci-Cerinic TI - Association of a Functional Polymorphism in the Matrix Metalloproteinase-12 Promoter Region with Systemic Sclerosis in an Italian Population AID - 10.3899/jrheum.100237 DP - 2010 Jul 01 TA - The Journal of Rheumatology PG - jrheum.100237 4099 - http://www.jrheum.org/content/early/2010/06/28/jrheum.100237.short 4100 - http://www.jrheum.org/content/early/2010/06/28/jrheum.100237.full AB - Objective To investigate the possible implication of the matrix metalloproteinase-12 (MMP-12) gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotype. Methods The MMP-12 rs2276109 A/G functional polymorphism was selected as a genetic marker and genotyped by polymerase chain reaction-restriction fragment length polymorphism assay in 513 unrelated subjects of Italian white ancestry: 250 patients with SSc [146 limited cutaneous SSc (lcSSc), 104 diffuse cutaneous SSc (dcSSc)] and 263 healthy individuals. Results A significant difference was observed in MMP-12 rs2276109 genotype distribution between patients with SSc and controls (p = 0.0003), and between lcSSc and dcSSc (p = 0.003). The A allele frequency was significantly higher in patients with SSc than in controls (p = 0.0002), and higher in dcSSc than in lcSSc (p = 0.003). After adjustment for age and sex, the homozygosity for the A allele significantly influenced the predisposition to SSc and to dcSSc (OR 2.44, 95% CI 1.61–3.71, p < 0.0001; OR 4.69, 95% CI 2.36–9.33, p < 0.0001, respectively). A trend toward an association between the AA genotype and lcSSc was observed (p = 0.06). The homozygosity for the A allele was also significantly and independently associated with antitopoisomerase I antibody positivity (OR 6.39, 95% CI 2.18–18.76, p = 0.001) and interstitial lung disease (OR 2.94, 95% CI 1.25–6.95, p = 0.01). Conclusion The MMP-12 rs2276109 gene polymorphism may contribute to susceptibility to SSc, and in particular to dcSSc and pulmonary fibrosis.