RESUMO
AIM: To investigate the relationships among diverse metalloproteases (MMPs) and their tissue inhibitors (TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus (HIV)-infected patients. METHODS: Single nucleotide polymorphisms (SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus (HCV) coinfection. A total of 158 patients were included, 57 of whom were HCV-coinfected. All patients drank < 50 g ethanol/day. Diverse SNPs (MMP-1 -1607 1G/2G, MMP-8 -799C/T, MMP-9 -1562 C/T, MMP-13 -77A/G, TNF-α -308 G/A, CCR5-∆32), and serum levels of MMPs (2, 3, 8, 9 and 10) and TIMPs (1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis (F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kPa. RESULTS: A total of 34 patients (21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2 (P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values (P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements (P = 0.01). Multivariate analyses showed that high levels of MMP-2 (OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2 (OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender (OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2. CONCLUSION: Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIV-infected patients with/without HCV coinfection.
RESUMO
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.