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GD Patients (gd + patient)
Selected AbstractsAnalysis of the glucocerebrosidase gene and mutation profile in 144 Italian gaucher patients,,HUMAN MUTATION, Issue 3 2002Mirella Filocamo Abstract Gaucher disease (GD), the most prevalent lysosomal storage disease characterized by a remarkable degree of clinical variability, results from deleterious mutations in the glucocerebrosidase gene (GBA). In this paper we report the molecular characterization of 144 unrelated Italian GD patients with the three types of the disease. The allelic frequencies of Italians are reported and the mutation profile is analyzed. Besides the common N370S, L444P, RecNciI, G202R, IVS2+1G>A, D409H, F213I mutations, the different molecular strategies, used for the mutation detection, identified the rare N107L, R131C, R170C, R170P, N188S, S196P, R285C, R285H, W312C, D399N, A446P, IVS10-1G>A, Rec,55, total gene deletion, as well as 12 mutant alleles that were exclusively present in the Italian population until now: the previously reported R353G, N370S+S488P mosaicism, IVS8(-11delC)-14T>A), Rec I, Y418C, and the seven novel alleles D127X, P159T, V214X, T231R, L354X, H451R, and G202R+M361I. The wide phenotypic differences observed within the genotypic groups as well as between siblings implicate a significant contribution of other modifying genetic and/or non-genetic factors and claim a comprehensive valuation of the patient including clinical., biochemical and molecular investigations for prognosis, appropriate interventive therapy and reliable genetic counseling. © 2002 Wiley-Liss, Inc. [source] Lack of association between pro-inflammatory cytokine (IL-6, IL-8 and TNF-,) gene polymorphisms and Graves' diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2005R.-H. Chen Summary Graves' disease (GD) is a common, autoimmune disease involving the thyroid gland, and it has been previously suggested that pro-inflammatory cytokines are involved in the disease's pathogenesis. The aim of this study was to test whether the interleukin (IL)-6 gene promoter region, or tumour necrosis factor (TNF)-, or IL-8 gene 3,-untranslated region (3,-UTR) polymorphisms could provide useful genetic markers for an individual's susceptibility to GD. A normal control group of 60 healthy people and 95 patients featuring GD were examined. Polymerase chain reaction (PCR)-based restriction analysis was performed for the three gene polymorphisms using endonucleases BsrBI, NcoI and ApaLI, respectively. We found no significant difference between the frequencies of genotype and allelic variants for the IL-6 gene promoter (,572 G/C), the TNF-, gene promoter (,308 A/G) and the IL-8 gene 3,-UTR (2767 A/G) for GD patients and for normal controls. Cytokines are a large group of proteins that may elicit multiple effects upon immunological reactions. It still appears to be very worthwhile to continue to aggressively search for cytokine gene polymorphisms in order to predict the development of such disease. [source] Association between the TAP2 gene codon 665 polymorphism and Graves' DiseaseJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 3 2006Rong-Hsing Chen Abstract A total of 95 patients with active Graves' disease (GD) and 105 normal healthy subjects were enrolled in this study, which attempted to determine whether single-site polymorphisms of the transporter associated with antigen processing 2 (TAP2) gene contribute to an individual's susceptibility to GD. Such polymorphisms were detected using polymerase chain reaction (PCR)-based restriction analysis. Associations between GD and the three site polymorphisms of the TAP2 gene at codons 379, 565, and 665 were investigated. The results of the genotype analysis revealed that the frequency of the GG homozygote's presence at codon 665 was lower, and that of the AA homozygote's presence was greater in GD patients (15.8% and 36.8%, respectively) compared to normal controls (34.3% and 16.2%, respectively; P<0.001). The OR (OD) for the risk of occurrence for the AA homozygote and AG heterozygote compared to the GG homozygote (as was the case for the GD patients) was respectively 4.941 and 2.117, with respective 95% confidence intervals (CI) of 2.303,10.598 and 1.020,4.369. The allelic analysis also demonstrated reduced G and enhanced A allele frequencies for GD patients compared to controls (respectively 39.5% vs. 59.0% [G allele], and 60.5% vs. 41.0% [A allele]; P=0.0001; OR=2.219, 95% CI: 1.449,3.395). By contrast, the differences between patient and control groups for the frequency of appearance of genotypes and allelic variants at codon 379 (P=0.522 and P=0.306, respectively) and codon 565 (P=0.199 and P=0.157, respectively) did not appear to be significant. These data reveal that the single-site polymorphism of the TAP2 gene at codon 665 may be an indicator for predicting GD development. J. Clin. Lab. Anal. 20:93,97, 2006. © 2006 Wiley-Liss, Inc. [source] Chaperone Activity of Bicyclic Nojirimycin Analogues for Gaucher Mutations in Comparison with N -(n -nonyl)DeoxynojirimycinCHEMBIOCHEM, Issue 17 2009Zhuo Luan Abstract Gaucher disease (GD), the most prevalent lysosomal storage disorder, is caused by mutations of lysosomal ,-glucosidase (acid ,-Glu, ,-glucocerebrosidase); these mutations result in protein misfolding. Some inhibitors of this enzyme, such as the iminosugar glucomimetic N -(n -nonyl)-1-deoxynojirimycin (NN-DNJ), are known to bind to the active site and stabilize the proper folding for the catalytic form, acting as "chemical chaperones" that facilitate transport and maturation of acid ,-Glu. Recently, bicyclic nojirimycin (NJ) analogues with structure of sp2 iminosugars were found to behave as very selective, competitive inhibitors of the lysosomal ,-Glu. We have now evaluated the glycosidase inhibitory profile of a series of six compounds within this family, namely 5- N,6- O -(N, -octyliminomethylidene-NJ (NOI-NJ), the 6-thio and 6-amino-6-deoxy derivatives (6S-NOI-NJ and 6N-NOI-NJ) and the corresponding galactonojirimycin (GNJ) counterparts (NOI-GNJ, 6S-NOI-GNJ and 6N-NOI-GNJ), against commercial as well as lysosomal glycosidases. The chaperone effects of four selected candidates (NOI-NJ, 6S-NOI-NJ, 6N-NOI-NJ, and 6S-NOI-GNJ) were further evaluated in GD fibroblasts with various acid ,-Glu mutations. The compounds showed enzyme enhancement on human fibroblasts with N188S, G202R, F213I or N370S mutations. The chaperone effects of the sp2 iminosugar were generally stronger than those observed for NN-DNJ; this suggests that these compounds are promising candidates for clinical treatment of GD patients with a broad range of ,-Glu mutations, especially for neuronopathic forms of Gaucher disease. [source] Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progressionCLINICAL ENDOCRINOLOGY, Issue 1 2010Kadija Yesmin Summary Objective, Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves' disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region. Design, A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region. Patients, A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort. Measurements, We used the ,2 -test to investigate association between the Tag SNPs and GD. Results, Association between the rs1801274 (P,= 0·003, OR = 1·12 [95% CI = 1·03,1·22] and rs6427598 (P = 0·012, OR = 0·90 [95% CI = 0·83-0·98]) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes. Conclusions, This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general. [source] Regulatory T cells in Graves' diseaseCLINICAL ENDOCRINOLOGY, Issue 4 2009Deshun Pan Summary Context, Graves' disease (GD) involves auto-immunity against thyroid cell antigens, but the reasons for induction of auto-immunity are uncertain. We wished to determine whether there was a deficiency of regulatory T cells in patients with active GD. Design, Venous blood samples were obtained from patients with GD before and after treatment, and controls, and peripheral blood mononuclear cells were prepared. Patients and measurements, Regulatory T cells were enumerated by Fluorescent Activated Cell sorting (FACS) in nineteen patients with untreated GD, 9 patients 6,8 weeks post RAI therapy, and 30 control subjects. Twenty-one patients with active GD prior to control of hyperthyroidism, 23 euthyroid controls without known autoimmune thyroid disease, and 10 patients who were euthyroid 6,12 months after RAI treatment were studied for expression of genes found in regulatory T cells by real-time Polymerase Chain reaction (PCR). Results, Percent distribution of CD4+, CD4+CD25+ and CD4+ CD25+int-hi CD127+lo regulatory T cells was similar in active GD patients and control subjects. The number of CD25+ and CD4+ CD25+int-hi CD127+lo cells was similar in GD patients and control subjects, but was lower in recently treated patients. Messenger RNA was prepared from PBMC, and reverse transcribed. Copy DNA abundance was evaluated by Real Time PCR using appropriate primers, for GAPDH (glyceraldehyde phosphate dehydrogenase) as a control housekeeping gene, and 5 genes related to function of regulatory T cells. Message RNA for Gadd45 alpha, Gadd45beta (growth arrest and damage inducible proteins), GITR (glucocorticoid inducible TNF receptor) and CD25 (IL-2R subunit) was more abundant in patients with active GD than in normal controls, and FoxP3 mRNA level was equal to that in controls. Message RNA levels in patients treated and euthyroid for 6 months were also greater than or equal to values in controls. Conclusion, This study provides evidence that there is no deficit in T regulatory cells during active GD, or during the months post therapy. [source] Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remissionCLINICAL ENDOCRINOLOGY, Issue 4 2007Anja K. Eckstein Summary Objective, To evaluate the relationship between severity of Graves' ophthalmopathy (GO) and relapse/remission rate of associated thyroid disease. Patients and methods, One hundred and fifty-eight patients with Graves' disease (GD) were seen within the first 6,12 months after the onset of GO and were followed for at least 18 months. During treatment, GO was classified as mild (n = 65) or severe course (n = 93) by severity and activity scores. All patients received standard anti-thyroid drug (ATD) treatment for 1 year, and in cases of relapse another cycle of ATD, thyroidectomy or radioiodine therapy. Results, Following ATD treatment, 27 patients (42%) with a mild course of GO went into thyroid disease remission, while only seven (8%) patients with a severe course of GO achieved remission (P < 0·0001). Eventually, 32 patients (49%) with a mild course needed definitive thyroid therapy and the remaining 9% preferred another cycle of ATD. However, among patients with a severe GO course, 84% needed definitive therapy (P < 0·0001) and 8% opted for another course of ATD treatment. The probability of relapse could also be predicted by TBII levels 12 months after initiation of ATD therapy, as 96·8% of patients with TBII levels above 7·5 IU/l relapsed (odds ratio 24·3). Conclusion, Patients with severe GO and high TBII are unlikely to go into remission. This allows early decision-making regarding definitive treatment of the thyroid in GD patients with severe GO or very high TBII levels. [source] | ||||||||||