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 MANETTI, MIRKO
A1 IBBA-MANNESCHI, LIDIA
A1 FATINI, CINZIA
A1 GUIDUCCI, SERENA
A1 CUOMO, GIOVANNA
A1 BONINO, CLAUDIA
A1 BAZZICHI, LAURA
A1 LIAKOULI, VASILIKI
A1 GIACOMELLI, ROBERTO
A1 ABBATE, ROSANNA
A1 BOMBARDIERI, STEFANO
A1 MONTECUCCO, CARLOMAURIZIO
A1 VALENTINI, GABRIELE
A1 MATUCCI-CERINIC, MARCO
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.