Association of metalloproteinase gene polymorphisms with systemic sclerosis in the European Caucasian population.
OBJECTIVE
Systemic sclerosis (SSc) is classified among the complex genetic disorders and is characterized by massive extracellular matrix deposits. These may be due to overactivation of transforming growth factor ss that may be in part a result of abnormal remodeling of extracellular matrix and microfibrils. Metalloproteinases (MMP) are a family of proteolytic enzymes, and MMP 2, 9, and 14 contribute to the degradation of microfibrils. Our aim was to determine whether polymorphisms of the MMP2, MMP9, and MMP14 genes confer susceptibility to SSc in a large population.


METHODS
A case-control study was performed in 659 SSc patients and 511 healthy matched controls from a European Caucasian population. Six Tag single-nucleotide polymorphisms (SNP) of the MMP2 gene and 2 SNP of MMP9 and MMP14 genes were genotyped.


RESULTS
All SNP were in Hardy-Weinberg equilibrium in the control population. There was no association between the MMP2, MMP9, and MMP14 variants we investigated and SSc for allelic and genotype frequencies. No association was observed for the different subphenotypes of SSc patients.


CONCLUSIONS
Our results in a large cohort of European Caucasian SSc patients do not support that MMP2, MMP9, and MMP14 genes are involved in the genetic background of SSc.
Wipff
Julien
J
Université Paris Descartes, AP-HP, Hôpital Cochin, France. julienwipff@cch.aphp.fr
Dieude
Philippe
P
Avouac
Jerome
J
Tiev
Kiet
K
Hachulla
Eric
E
Cracowski
Jean-Luc
JL
Diot
Elizabeth
E
Sibilia
Jean
J
Mouthon
Luc
L
Meyer
Olivier
O
Kahan
Andre
A
Boileau
Catherine
C
Allanore
Yannick
Y
D000368:Aged; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D020894:Microfibrils / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D044465:White People / Q000235:genetics*
D016212:Transforming Growth Factor beta; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14