title: Association of MMP-8 promoter gene polymorphisms with carotid atherosclerosis: preliminary study.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) are involved in the remodeling of the extracellular matrix in the arterial wall. Collagen I is associated with vascular smooth muscle cell (VSMC) migration and monocyte differentiation. MMP-8 is expressed in atherosclerotic plaque and preferentially cleaves collagen type I. The aim of this study was to investigate the associations of two MMP-8 promoter polymorphisms, rs11225395 (-799C/T) and rs1320632 (-381 A/G), with carotid plaque occurrence, and the influence of these polymorphisms on MMP-8 mRNA expression in plaque tissue.
  
  
  METHODS
  The study included a total of 766 participants: 277 controls and 489 patients with carotid atherosclerosis undergoing endarterectomy. The two investigated polymorphisms were genotyped by PCR-RFLP. The gene expression analysis was performed by real-time PCR.
  
  
  RESULTS
  In females only, a significantly higher frequency of the -381G allele was found in patients with carotid atherosclerosis compared to controls (OR, 1.7; 95% CI 1.1-2.9; p = 0.001). Significant up-regulation of MMP-8 gene expression was observed in patients carrying the -381G allele compared to those with the AA genotype (mean factor, 3.54; S.E. range, 0.643-19.551; p = 0.007). Carotid plaque tissue of the haplotype G(-381)T(-799) showed a significantly higher mRNA level compared with the reference A(-381)C(-799) haplotype (p = 0.003).
  
  
  CONCLUSIONS
  Our preliminary results indicate that MMP-8 -381A/G and -799C/T gene polymorphisms could be risk factors for carotid atherosclerosis. Further validation and functional studies are needed to establish the potential regulatory role of these polymorphisms and their impact on susceptibility to carotid atherosclerosis.
authors: VINČA Institute of Nuclear Sciences, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia. tamariska@vinca.rs
authors: Tamara
authors: T
authors: Djurić
authors: Aleksandra
authors: A
authors: Stanković
authors: Igor
authors: I
authors: Končar
authors: Djordje
authors: D
authors: Radak
authors: Lazar
authors: L
authors: Davidović
authors: Dragan
authors: D
authors: Alavantić
authors: Maja
authors: M
authors: Živković
mesh_terms: D000328:Adult; D000368:Aged; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D055771:Serbia; D014463:Ultrasonography
chemical_list: D012333:RNA, Messenger; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8