Abstract 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.

Association of a functional polymorphism in the matrix metalloproteinase-12 promoter region with systemic sclerosis in an Italian population / M. Manetti; L. Ibba-Manneschi; C. Fatini; S. Guiducci; G. Cuomo; C. Bonino; L. Bazzichi; V. Liakouli; R. Giacomelli; R. Abbate; S. Bombardieri; C. Montecucco; G. Valentini; M. Matucci-Cerinic. - In: THE JOURNAL OF RHEUMATOLOGY. - ISSN 0315-162X. - STAMPA. - 37:(2010), pp. 1852-1857.

Association of a functional polymorphism in the matrix metalloproteinase-12 promoter region with systemic sclerosis in an Italian population

MANETTI, MIRKO
;
IBBA, LIDIA;FATINI, CINZIA;GUIDUCCI, SERENA;ABBATE, ROSANNA;MATUCCI CERINIC, MARCO
2010

Abstract

Abstract 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.
2010
37
1852
1857
Goal 3: Good health and well-being for people
M. Manetti; L. Ibba-Manneschi; C. Fatini; S. Guiducci; G. Cuomo; C. Bonino; L. Bazzichi; V. Liakouli; R. Giacomelli; R. Abbate; S. Bombardieri; C. Mon...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/394222
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