Role of plasma matrix-metalloproteases (MMPs) and their polymorphisms (SNPs) in sepsis development and outcome in ICU patients.
Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs), modulated by different single nucleotide polymorphisms (SNPs), are critical in sepsis development. Ninety ICU severely septic and 91 ICU uninfected patients were prospectively studied. MMP-1 (-1607 1G/2G), MMP-3 (-1612 5A/6A), MMP-8 (-799 C/T), MMP-9 (-1562 C/T), and MMP-13 (-77A/G) SNPs were genotyped. Plasma MMPs (-1, -2, -3, -8, -9, -10, -13) and TIMPs (-1,-2,-4) were measured. AA homozygotes and A allele carriers of MMP-13 (-77 A/G) and 1G2G carriers of the MMP-1 (-1607 1G/2G) SNPs frequencies were different between septic and uninfected patients (p < 0.05), as well as plasma MMP-3, -8, -9 -10 and TIMP-2 levels (p < 0.04). No differences in MMPs levels among MMP-13 or MMP-1 SNPs genotypes carriers were observed. The area under the ROC curve for MMP-8 in the diagnosis of sepsis was 0.87 (95% CI 0.82-0.92), and that of CRP was 0.98 (0.94-0.998), whereas the area of MMP-9 in the detection of non-septic state was 0.73 (0.65-0.80), p < 0.0001 for all curves. Sepsis associated with increased MMP-8 and decreased MMP-9 levels in multivariate analysis (p < 0.0002). We report for the first time an association between MMP-13 and MMP-1 SNPs and sepsis. An independent association of MMP-8 and MMP-9 levels with sepsis was also observed.
Critical Care, Hospital Universitario Central de Asturias (HUCA).
Guadalupe
G
Martin
Infectious Diseases, Hospital Universitario Central de Asturias (HUCA).
Víctor
V
Asensi
Biochemistry and Molecular Biology, Oviedo University School of Medicine, Oviedo.
A Hugo
AH
Montes
Infectious Diseases, Hospital de Galdacano, Vizcaya, all in Spain.
Julio
J
Collazos
Molecular Genetics Unit-Nephrology Research Institute, Hospital Universitario Central de Asturias (HUCA).
Victoria
V
Alvarez
Infectious Diseases, Hospital Universitario Central de Asturias (HUCA).
José A
JA
Carton
Critical Care, Hospital Universitario Central de Asturias (HUCA).
Francisco
F
Taboada
Biochemistry and Molecular Biology, Oviedo University School of Medicine, Oviedo.
Eulalia
E
Valle-Garay
D000368:Aged; D000483:Alleles; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018805:Sepsis / Q000097:blood / Q000209:etiology* / Q000235:genetics*
D020782:Matrix Metalloproteinases