Polymorphisms of pro-inflammatory cytokine genes could take part in IVDD pathophysiology as the result of alteration in their expression levels or structures. The current study indicated significant roles of TNF-α -308 G/A and TNF-α -238 G/A SNPs with IVDD among Iranian patients. However, this study did not show any significant association between IVDD and either of SNPs of IL-1 and IL-6 genes.
BackgroundConsidered as one of the major causes of low back pain, Intervertebral disc degeneration (IVDD) is caused by several genetic and environmental factors. As inflammation plays an important role in disc degeneration, the genetic changes in both inflammatory and anti-inflammatory genes may play causative roles in IVDD as well. Therefore, the interactions between inflammatory and anti-inflammatory cytokines and also other components of disc matrix would determine the degree of tissue destruction in disc degeneration. However, there is still controversy regarding the exact role of inflammation and disc homeostasis imbalance in pathophysiology of IVDD. Therefore, current study was conducted to investigate the role of IL-10 and TGF-β single nucleotide polymorphisms (SNP) in Iranian IVDD patients.MethodsSeventy-six IVDD patients and 140 healthy controls were enrolled in this study. Genomic DNA from peripheral leukocytes was tested for 3 SNPs in IL10 (L-10 -1082G/A (rs1800896), IL-10 -819C/T (rs1800871), IL-10 -592A/C (rs1800872)) and 2 SNPs in TGF-β (TGF-β Codon 10 C/T (rs1982037), and TGF-β Codon 25 C/T (rs1800471) genes through PCR-SSP method. The extracted genomic DNA was genotyped for the aforementioned SNPs of interest using specific primers, which were coated in the cytokines KITs and based on the PCR-SSP method for sequencing.ResultsThe ‘T’ allele of IL-10 -819C/T and the ‘C’ allele of IL-10 -592A/C were more prevalent among patients, whereas the ‘C’ and ‘A’ alleles of respective SNPs were significantly more frequent in controls. The genotypes including ‘CT’ of IL-10 -819C/T, ‘CA’ of IL-10 -592A/C, and ‘GA’ of IL-10 -1082A/G were more common among patients, while the ‘CC’ genotype of both IL-10 -819C/T and IL-10 -592A/C SNPs were more frequent in controls. In addition, the IL-10 haplotypes including ‘ACC’, ‘ATA’, and ‘ACA’ were significantly associated with disease. Meanwhile, the ‘TC’ haplotype of TGF-β was more common among patients as well.ConclusionsThe IL-10 SNPs were significantly associated with IVDD in Iranian population; which proposes that genomic alterations of anti-inflammatory cytokines could lead to homeostasis imbalance in intervertebral discs and degenerative changes.
Background: Collagens are the main components of the extracellular matrix of intervertebral discs. The genetic mutations in collagen genes could potentially play a causal role in pathophysiology of intervertebral disc degeneration (IVDD). In this study, we investigate the association of COL1A1 and COL9A2 single nucleotide polymorphisms (SNPs) with IVDD. Material and Methods: ninety-six Iranian IVDD patients and 94 controls matched for age and sex were included. 5 cc of peripheral blood samples were obtained for DNA extraction using the Phenol-Chloroform method. The primers for SNPs COL1A1 rs909102 and COL9A2 were designed based on the TaqMan protocol and genotyped by real-time PCR with TaqMan. Results: The 'T' allele, 'CC' and 'TT' genotypes of COL1A1 rs909102 were more common among patients, however not significantly. Despite the similar allele distribution of COL9A2 rs137853213 in patients and controls, the homozygote genotypes were more frequent among patients, though this was not significant either. Conclusion: The allele and genotype distributions of COL1A1 rs909102 and COL9A2 rs137853213 SNPs were not significantly associated with IVDD in an Iranian population.
Background: Intervertebral disc degeneration (IVDD) is a multifactorial disease that is sensitive to the balance between anti-inflammatory and pro-inflammatory cytokines. This study investigated the single nucleotide polymorphisms (SNPs) of interleukin 4 (IL-4) in IVDD. Methods: Genomic DNA of peripheral mononuclear cells of 76 IVDD patients and 140 healthy controls were investigated for three SNPs of IL-4 (rs2243248 (−1098G/T), rs2243250 (−590 C/T), rs2070874 (−33 C/T)) and 1 SNP of IL-4RA (rs180275, +1902 A/G) through PCR-SSP method. Results: The 'C' allele frequency of IL-4 rs2243250 was 104 in 76 patients, while it was 149 in 140 controls (OR = 2, p =.001); also this SNP was significantly associated with post-operative pain reduction. The 'C' allele of IL-4 rs2070874 (130 in 76 patients, and 200 in 140 controls, OR = 2.66), and the 'CC' genotype were more frequent among patients (OR = 3.98, p <.001) than controls. 'TTT' haplotype was more common in controls (OR = 0.36, p <.001) and 'TCC' was also more common in patients (OR = 1.75, p =.012). A meta-analysis of previous studies found significantly higher IL-4 levels in disc tissues of IVDD patients, which was not similarly found in blood samples. Conclusion: The immune system plays an important role in IVDD. The extent and progress of the disease vary significantly with IL-4 level. Meanwhile, the rs2070874 and rs2243250 SNPs of IL-4 were significantly associated with IVDD in Iranian patients.
Background: Intervertebral disc degeneration (IVDD) is an age-related degenerative disease, presenting with low back pain or radicular pain. The inflammatory changes would occur in discs in the process of IVDD. Therefore, the inflammatory and anti-inflammatory cytokines, as well as their respective genes, have been proposed to play roles in pathophysiology of disease. This study has been conducted to elucidate the role of IL-2, IL-12, and IFN-γ single nucleotide polymorphisms (SNP) in this disease. Method: Seventy-six patients who were diagnosed with IVDD and 140 healthy controls who complied with eligibility criteria were included. A total volume of 5 cc peripheral blood was obtained from each participant to investigate the IL-2 + 166G/T, IL-2-330G/T, IL-12 − 1188A/C, and IFN-γ +847A/T SNPs through PCR-SSP method. Results: The 'TG' and 'TT' genotypes of IL-2 − 330G/T polymorphism were significantly more common among patients and healthy controls respectively. The 'GT' and 'TT' haplotypes of IL-2 (comprised of-330G/T, and + 166G/T SNPs) were also more common among patients and controls respectively. Conclusion: This study indicated the significant role of IL-2 genotypes and haplotypes in IVDD. These SNPs were differently distributed in patients and controls. Therefore, alteration in the structure of IL-2 gene could play an important role in pathophysiology of IVDD.
OBJECTIVE While microsurgery has been proposed as the first-line treatment for patients with low-grade (Spetzler-Martin grade I or II) brain arteriovenous malformations (bAVMs), recent studies have shown promising results for endovascular treatment (EVT) as a single proper choice for the management of this group of bAVMs. In this study, the authors evaluated the safety and efficacy of EVT as a first-line strategy for curing low-grade bAVMs at their center. METHODS All patients with low-grade bAVMs managed primarily by EVT between 2015 and 2021 were enrolled in this study. Patients were evaluated and treated by the same team and followed with the same protocol. The primary endpoint was the efficacy of EVT on the cure of low-grade bAVMs. The second endpoint was the safety of EVT for the treatment of low-grade bAVMs, including procedural complications and long-term clinical outcomes. RESULTS A total of 109 patients were enrolled and represented in the study population. The mean patient age was 31.6 ± 14.8 years. Forty-eight AVMs (44%) were Spetzler-Martin grade I and 61 (56%) were grade II. Of 99 patients who completed their EVT sessions, complete exclusion was achieved in 89 patients (89.9%). Overall, complete exclusion was achieved in 59.6% of patients after a single EVT session. At the 6-month follow-up, 106 patients (97.2%) had a favorable outcome. Four patients (4.6%) experienced transient neurological deficits, and 1 patient (0.9%) had a permanent neurological deficit. CONCLUSIONS EVT can be offered as the first choice of treatment for select patients with low-grade bAVMs, with a high cure rate and low morbidity.
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