title: The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP) and tissue inhibitor (TIMP) plasma levels in different infectious and non-infectious conditions.
abstract: Matrix metalloproteases (MMPs) are increased in different infections due to their role in controlling immune responses and are regulated by tissue inhibitors (TIMPs). Different MMP promoter single nucleotide polymorphisms (SNPs) induce changes in MMP genes, mRNA and protein expression. Gender might also modify MMP plasma levels. In order to determine the weight of these variables on MMP secretion we studied MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4 plasma levels in 90 patients with severe bacterial sepsis, 102 with anti-retroviral (ARV)-treated HIV monoinfection, 111 with ARV-treated HIV-hepatitis C virus (HCV) co-infection and 86 non-infected controls (45 stroke and 41 trauma patients). MMP-1(-1607 1G/2G), MMP-3(-1612 5A/6A), MMP-8(-799C/T), MMP-9(-1562 C/T) and MMP-13(-77A/G) SNPs were genotyped. MMP-3 plasma levels were significantly higher in men than in women in each diagnostic group, and MMP-3 SNP allele 6A carriers also had higher levels than allele 5A carriers, an effect that was magnified by sepsis. Independent predictors of higher MMP-3 levels were male gender (P = 0.0001), MMP-3(-1612 5A/6A) SNP (P = 0.001), higher levels of TIMP-4 (P = 0.004) and MMP-8 (P = 0.006) and lower levels of MMP-1 (P = 0.03) by multivariate analysis. No strong associations with gender or SNPs were observed for other MMPs or TIMPs. In conclusion, male gender and MMP-3(-1612 5A/6A) 6A allele carriage increased MMP-3 plasma levels significantly, especially in patients with severe bacterial sepsis. This confounding gender effect needs to be addressed when evaluating MMP-3 plasma levels in any infectious or non-infectious condition.
authors.affiliation: Infectious Diseases, Hospital De Galdacano, Vizcaya.
authors.forename: J
authors.initials: J
authors.lastname: Collazos
authors.affiliation: Infectious Diseases, Hospital Universitario Central de Asturias (HUCA), Oviedo University School of Medicine, Oviedo, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Asensi
authors.affiliation: Critical Care, Hospital Universitario Central de Asturias (HUCA), Oviedo University School of Medicine, Oviedo, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Martin
authors.affiliation: Biochemistry and Molecular Biology, Hospital Universitario Central de Asturias (HUCA), Oviedo University School of Medicine, Oviedo, Spain.
authors.forename: A H
authors.initials: AH
authors.lastname: Montes
authors.affiliation: Infectious Diseases, Hospital Universitario Central de Asturias (HUCA), Oviedo University School of Medicine, Oviedo, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Suárez-Zarracina
authors.affiliation: Biochemistry and Molecular Biology, Hospital Universitario Central de Asturias (HUCA), Oviedo University School of Medicine, Oviedo, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Valle-Garay
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D060085:Coinfection / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D006526:Hepatitis C / Q000097:blood / Q000235:genetics / Q000821:virology; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D018805:Sepsis / Q000097:blood / Q000235:genetics; D012737:Sex Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*
chemical_list: D044966:Anti-Retroviral Agents; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3
keywords: HIV; MMPs; TIMPs; bacterial; gender; hepatitis C; human; polymorphisms; sepsis