title: Matrix metalloproteinase-2, -9, -12, and tissue inhibitor of metalloproteinase 2 gene polymorphisms and cutaneous expressions in patients with Behçet's disease.
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.
authors.affiliation: Department of Biology, Sungshin Women's University, Seoul, Korea.
authors.forename: K S
authors.initials: KS
authors.lastname: Park
authors.forename: Y
authors.initials: Y
authors.lastname: Min
authors.forename: S R
authors.initials: SR
authors.lastname: Park
authors.forename: E H
authors.initials: EH
authors.lastname: Kim
authors.forename: D J
authors.initials: DJ
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Bang
authors.forename: E-S
authors.initials: ES
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001528:Behcet Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004893:Erythema Nodosum / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D056910:Republic of Korea; D012867:Skin / Q000378:metabolism / Q000473:pathology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
chemical_list: C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053508:Matrix Metalloproteinase 12