Serum TIMP1 and TIMP2 concentration in patients with different grades of meningioma.

OBJECTIVE: Meningiomas are common primary brain tumors that constitute about 13% of all intracranial tumors. Matrix metalloproteinase-9 (MMP-9) is able to degrade the extracellular matrix and basement membrane leading to cancer cell invasion and metastasis. MMPs are specifically inhibited by a family of small extracellular proteins known as the tissue inhibitors of metalloproteinases (TIMPs). The objective of this project was to evaluate serum concentration of TIMP-1 and TIMP-2 in patients with different grades of meningioma. PATIENTS AND METHODS: Ninety samples from different stages of patients with meningitis (42 cases of grade I, 28 grade II, 20 grade III) and 51 samples from normal healthy were included in this study. Total protein concentration (TPC) and the level TIMP-1 and TIMP-2 serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: No significant change in the TPC was seen in the serum of patients with meningioma when compared with normal controls. Results obtained demonstrated that all serum samples presented TIMP-1 and TIMP-2 expression, whereas, starting from grade I to III meningiomas, a significant decrease of TIMP-1 and TIMP-2 expression was observed as compared to controls. CONCLUSION: The results of this study show that a low expression of TIMP1 and TIMP2 is correlated with advanced stages of meningioma. It is also concluded that the detection of serum TIMP1 and TIMP2 may be useful in classifying different grades of meningioma.

VDR and GC gene polymorphisms modulate the risk of lumbar disc degeneration in Iran.

OBJECTIVE: Lumbar disc degeneration (LDD) occurs commonly in humans. Vitamin D metabolic and signaling pathway plays a significant role in intervertebral disc degeneration. The aim of this study was to evaluate the influence of the genetic polymorphism in the two key genes of 1,25-(OH)2-D3 pathway, VDR (vitamin D receptor) and GC (group-specific component), in LDD development. PATIENTS AND METHODS: Two single-nucleotide polymorphisms, VDR rs2228570 (FokI) and GC rs7041, were genotyped in 180 patients with LDD and 230 healthy individuals. Genomic DNA was extracted from whole peripheral blood. VDR and GC genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A significant difference in genotype distributions of rs2228570 in VDR and rs7041 in GC gene were observed between cases and controls (P = .01 and. 005, respectively). The VDR AA homozygous genotype was seen in 30(16.7%) patients with LDD and 20(8.7%) controls (codominant model: OR = 2.48; 95% CI 1.30-4.73, P = .005) with an estimated approximately 2.5-fold risk of developing LDD in individuals with this genotype. Moreover, higher grades of disc degeneration were more related to VDR A allele. The minor allele of GC rs7041 was associated with a decreased risk of LDD (OR = 0.69; 95% CI 0.44-0.82, P = .001). CONCLUSION: In conclusion, our results suggest for the first time that the genetic variants of VDR and GC genes contribute to genetic predisposition to LDD in Iran. These findings need further validation in the large multicenter case-control studies.

Genetic Dimension of Intervertebral Disc Degeneration: Polymorphism of Matrix Metalloproteinase 1 and 3 in the North Iranian Population.

AIM: The etiology of intervertebral disc degeneration is still vague and both genetic and environmental factors are assumed as the main causes. One of the proposed genetic factors is the polymorphism of matrix metalloproteinases (MMPs) genes. The aim of this study was to explore the relationship between two polymorphisms (MMP-1-755 T/G [rs498186] and MMP-3 A/C [rs632478]) and disc degeneration. MATERIAL AND METHODS: We performed a case-control study on 130 cases with intervertebral disc degeneration confirmed by magnetic resonance imaging (MRI) and 210 healthy individuals. The Schneiderman criterion was used to determine the severity of the disc degeneration. Blood samples were collected from the participants. The genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratios and 95% CIs were determined as measures of the strength of association between genotypes and disc degeneration. RESULTS: The most frequent intervertebral disc degeneration was observed in age range of 31-40 years (43.2%). A significant association was found between the MMP-3 polymorphism and disc degeneration (p < 0.001). The homozygote CC was associated with an increased risk of disc degeneration compared with the AA genotype (OR=5.25; 95%CI=2.82-9.77, p < 0.001). We did not find any significant association of the MMP-1 polymorphism with disc degeneration (p=0.95). CONCLUSION: The MMP-3 [rs632478] polymorphism may contribute to susceptibility to disc degeneration. To confirm our findings, additional well-designed studies in diverse ethnic populations are required.