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


CONCLUSIONS
The MMP-12 rs2276109 gene polymorphism may contribute to susceptibility to SSc, and in particular to dcSSc and pulmonary fibrosis.
Manetti
Mirko
M
Department of Anatomy, Histology and Forensic Medicine, University of Florence, Viale G.B. Morgagni 85, I-50134, Florence, Italy. mirkomanetti@yahoo.it
Ibba-Manneschi
Lidia
L
Fatini
Cinzia
C
Guiducci
Serena
S
Cuomo
Giovanna
G
Bonino
Claudia
C
Bazzichi
Laura
L
Liakouli
Vasiliki
V
Giacomelli
Roberto
R
Abbate
Rosanna
R
Bombardieri
Stefano
S
Montecucco
Carlomaurizio
C
Valentini
Gabriele
G
Matucci-Cerinic
Marco
M
D000328:Adult; D000368:Aged; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012595:Scleroderma, Systemic / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology
D005819:Genetic Markers; D053508:Matrix Metalloproteinase 12