functional polymorphism of the granulocyte macrophage colony stimulating factor is not associated with the outcome of HTLV-I infection

Genetic background has known to be associated with the outcome of human T cell lymphotropic virus [HTLV] type I infection. In The present study we investigate the association between GM-CSF gene polymorphisms with the outcome of HTLV-I infection. We analyzed 3 single-nucleotide polymorphisms in the promter region of granulocyte macrophage colony stimulating factor [GM-CSF] at positions -677A/C, -1440A/G and -1916T/C in 68 patients with HTLV- I-associated myelopathy/tropical spastic paraparesis [HAM/TSP] and 77 HTLV-I-seropositive asymptomatic carriers and 175 healthy controls from an area in Iran, Mashhad, where HTLV-I is endemic. No significant differences were observed in the distribution of GM-CSF polymorphisms between HAM/TSP patients, HTLV-I carriers and healthy controls [P> 0.05]. The -611A/C polymorphism fall within the transcriptional enhancer factor-2 [TEF-2] binding site, so an electrophoretic mobility shift assay [EMSA] was performed to determine the effects of polymorphisms on protein binding to the GM-CSF promoter. The result showed a significantly higher binding efficiency of nuclear protein to the A allele compared with the C allele. Our study suggests that polymorphisms in the GM-CSF promoter is not associated with the outcome of HTLV-I infection, however, GM-CSF polymorphism at position -677 could indeed influence gene expression

Evaluation of specific purified TCR effect on the immunoregulatory potential of TGF-Beta

Transforming growth factor beta [TGF-beta] is a mediator released by nearly all cell types. It has suppression activity on the immune system, but exactly how this effect is carried out is not clear. Previous experiments showed that IgG interacts with or carriers active TGF-P, that could suppresses cytotoxic T-cell responses to an immunogenic tumor in mice. Since T cell receptor [TCR] has structural similarities with IgG, we asked the question-whether a specific TCR could interfere with and enhance the suppressive effect of TGF-P on T-cell proliferation. T-cell lines were established by limiting dilution and specific TCR were extracted and purified. Mixed lymphocyte reaction [MLR] was carried out using DA [RT1a] vs. LEW [RT11] lymph node cells and DA vs. PVG [RT1u] lymph node cells. DA cells were used as responder cells and PVG/LEW as stimulator cells. Proliferation of DA cells was examined with different concentration of TGF-beta by adding 1 micro ci 3 H-thymidine 24 hours prior to harvesting the cells. The results showed that the presence of a specific TCR does not have any effect on the percentage of suppression when already fully suppressed by TGF-P. However, it does have an effect on TGF-beta stimulated suppression under certain conditions. When TCR was added at the same concentration as TGF-beta [1-2 ng/ml], inhibited TGF-P stimulated suppression of proliferation, but when added at higher concentration than TGF-P, this effect disappeared, and the proliferation was suppressed in the same way, as TCR was absent. Thus, TCR interaction with TGF-beta could play an important role in the homeostasis of immunity by augmenting the proliferation of activated dominant lymphocyte clones. This would promote suppression of activation/proliferation of new specific antigen- reactive clones that may arise during ongoing immunity, and suppressing some autoimmune diseases

Genetics of diabetic neuropathy: study of VEGF gene

Vascular factors in conjunction with metabolic issues are involved in both etiopathogenesis of diabetic neuropathy [DNU], and more remarkably in [repair] phase, when the net balance between neuroregenerative/degenerative reactions is dictated to some extent by these factors. The ischemic nature of DNU indicates the importance of re-establishment of blood vessels. VEGF, a growth factor which, in addition to its hemodynamic effects, possesses an [angiogenic] capacity has been the subject of extensive investigations in DNU, especially, interventional therapies. The impacts of racial and inherited backgrounds in the development of DNU suggest that the genetic issues partially govern the outcome of diabetic late complications, including DNU. By conducting a candidate gene case-control association study, present study explores the possibility if the inter-individual variations of VEGF gene structure by any means encode the genetic susceptibility/resistance in the course of DNU. The distribution of VEGF gene polymorphisms frequencies were analyzed at positions -7[*]C/T, -1001 [*]G/C, -1154[*]G/A and -2578[*]C/A and were evaluated by ARMS-PCR in 248 type 1 diabetic subjects [81 DNU[+], 167 DNU[-] and 113 healthy controls, all from [British-Caucasian] origin. When the frequency of the polymorphic alleles/genotypes between patients and controls, and also between two subgroups within patients' group with each other [DNU[+] vs. DNU[-]] or with healthy controls were compared, only in one situation a significant difference was evident. The distribution of a VEGF gene polymorphism at promoter region [-7[*]C/T] at allelic [but not at genotypic] level was notably different between diabetics, with and without neuropathy, while the minor allele [T] conferred a protective effect [P=0.03; OR = 1.75]. The present study may imply a prognostic value for VEGF gene polymorphism at promoter region [-7[*]C/T] in DNU. However, it requires further studies to appreciate better the phenotypic impact of this polymorphism in this chronic complication of diabetes. A catalog of candidate genes polymorphisms that functionally reflect a protection/predisposition to DNU can provide the genotypic profile that can be useful to reasonably predict the overall behavior of diabetic subjects to the metabolic derangements relative to development of DNU, which in turn may require adoption of relevant preventive and therapeutic measures