A functional polymorphism in MMP1 could influence osteomyelitis development.
Osteomyelitis (OM) is a bone infection characterized by necrosis and new formation of bone. Because matrix metalloproteases (MMPs) play an important role in bone extracellular matrix remodeling, we investigated the role of some MMP polymorphisms in OM patients. A total of 118 OM patients and 300 blood donors were genotyped for the polymorphisms of MMP1 (-1607 1G/2G) and MMP13 (-77A/G). Levels of MMPs (-1, -2, -3, -8, -9, -10, and -13) and tissue inhibitors of metaloproteases (TIMP-1, -2, and -4) in serum and in human osteoblasts obtained from OM biopsies also were determined. The MMP1 (-1607 2G/2G) genotype was significantly more frequent among OM patients compared with controls [65.3% versus 33.7%, chi(2) = 26.85, odds ratio (OR) = 3.24, 95% confidence interval (CI) 2.03-5.2, p < .0001]. The MMP1 2G allele also was more frequent in OM patients (73.3% versus 57.2%, chi(2) = 37.76, OR = 2.75, 95% CI 1.96-3.85, p < .0001). Carriers of the 2G allele had significantly higher osteoblast MMP1 mRNA and MMP-1 serum levels than noncarriers (p < .04). Interleukin 1alpha (IL-1alpha) increased MMP-1 and -13 protein secretion and Ets1 mRNA expression by OM patients' osteoblasts. No association of the MMP13 (-77 A/G) polymorphism with OM was observed. The MMP1 (-1607 1G/2G) polymorphism might contribute to OM pathogenesis. This could be due to increased expression of MMP-1 by osteoblasts and is regulated by IL-1alpha.
Montes
Angel Hugo
AH
Departamento de Bioquímica y Biologia Molecular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.
Valle-Garay
Eulalia
E
Alvarez
Victoria
V
Pevida
Marta
M
García Pérez
Eva
E
Paz
Jose
J
Meana
Alvaro
A
Asensi
Victor
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D053506:Matrix Metalloproteinase 10 / Q000097:blood; D053509:Matrix Metalloproteinase 13 / Q000097:blood / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020784:Matrix Metalloproteinase 8 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010019:Osteomyelitis / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1 / Q000032:analysis; D019714:Tissue Inhibitor of Metalloproteinases; D055815:Young Adult
C494041:ETS1 protein, human; D053582:Interleukin-1alpha; D050784:Proto-Oncogene Protein c-ets-1; D019714:Tissue Inhibitor of Metalloproteinases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1