RT Journal Article SR Electronic T1 Association of a Functional Polymorphism in the Matrix Metalloproteinase-12 Promoter Region with Systemic Sclerosis in an Italian Population JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP 1852 OP 1857 DO 10.3899/jrheum.100237 VO 37 IS 9 A1 MIRKO MANETTI A1 LIDIA IBBA-MANNESCHI A1 CINZIA FATINI A1 SERENA GUIDUCCI A1 GIOVANNA CUOMO A1 CLAUDIA BONINO A1 LAURA BAZZICHI A1 VASILIKI LIAKOULI A1 ROBERTO GIACOMELLI A1 ROSANNA ABBATE A1 STEFANO BOMBARDIERI A1 CARLOMAURIZIO MONTECUCCO A1 GABRIELE VALENTINI A1 MARCO MATUCCI-CERINIC YR 2010 UL http://www.jrheum.org/content/37/9/1852.abstract 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.