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Matrix metalloproteinase-2, -9, -12, and tissue inhibitor of metalloproteinase 2 gene polymorphisms and cutaneous expressions in patients with Behçet's disease

Authors
Park, KS; Min, Y; Park, SR; Kim, EH; Lee, DJ; Bang, D; Lee, ES
Citation
Tissue antigens, 79(5):333-339, 2012
Journal Title
Tissue antigens
ISSN
0001-28151399-0039
Abstract
Matrix metalloproteinases (MMPs) induce leukocyte migration into inflammation sites that lead to either promotion or repression of inflammation by activating or inactivating cytokines. An increased level of MMP-9 and a decreased level of MMP-2 have been observed in Behçet's disease (BD). This study was performed to analyze the relationship between MMP-2, -9, -12 and the tissue inhibitor of metalloproteinase-2 (TIMP-2) promoter polymorphisms in developing BD. The expression of MMP-2 and -9 was also evaluated in the skin of BD. The MMPs and TIMP-2 polymorphisms were confirmed by using polymerase chain reaction-restriction fragment length polymorphism in 251 BD and 312 controls. Cutaneous expression of MMP-2 and -9 in 17 BD patients with erythema nodosum (EN) or EN-like lesion was compared with 14 patients with idiopathic EN by immunohistochemical stains. The frequency of MMP-2-1575*G/*G and MMP-2-735*C/*C genotypes was shown to be lower in BD, whereas MMP-9-1562*C/*C was significantly higher in BD compared with the controls. The frequency of common haplotype MMP-2-1575*G -735*C was significantly lower in BD patients than in controls (P = 0.0046, permutation P = 0.009). No significant differences were observed between BD and controls in the allele and genotype frequencies of MMP-12-82A>G or TIMP-2-418G>C polymorphisms. The tissue expression of MMP-2, shown by immunohistochemistry, was significantly lower in BD compared with the controls. However, the expression of MMP-9 was significantly higher in BD. These results suggest that MMP-2 and -9 could each modulate the development of BD in opposite directions. Major genotypes of the MMP-2-1575*G/*G and MMP-2-735*C/*C and the common MMP-2-1575*G -735*C haplotype may provide some protection against development of BD, while MMP-9-1562*C/*C may promote the disease. The reciprocal expression of MMP-2 and -9 in the skin tissue of BD was also confirmed.
MeSH terms
AdolescentAdultAgedAllelesAsian Continental Ancestry Group/geneticsBehcet Syndrome/complications/*genetics/pathologyCase-Control StudiesErythema Nodosum/complications/*genetics/pathologyFemaleGenotypeHaplotypesHumansMaleMatrix Metalloproteinase 12/*geneticsMatrix Metalloproteinase 2/*geneticsMatrix Metalloproteinase 9/*geneticsMiddle AgedPolymerase Chain ReactionPolymorphism, GeneticPolymorphism, Restriction Fragment LengthPromoter Regions, GeneticRepublic of KoreaSkin/metabolism/pathologyTissue Inhibitor of Metalloproteinase-2/*genetics
DOI
10.1111/j.1399-0039.2012.01863.x
PMID
22428754
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Dermatology
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이, 은소
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