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1.
V. Pravica A. Asderakis C. Perrey A. Hajeer P.J. Sinnott I.V. Hutchinson 《International journal of immunogenetics》1999,26(1):1-3
The DNA sequence of the human IFN-γ gene shows the presence of a variable-length CA repeat in the first intron of the gene. We investigated the allele distribution of this microsatellite region in 164 unrelated healthy individuals, and the association with interferon-γ (IFN-γ) production. In vitro production of IFN-γ showed a significant correlation with the presence of allele #2. 相似文献
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A CA repeat polymorphism of the IFN-gamma gene is associated with susceptibility to type 1 diabetes. 总被引:7,自引:0,他引:7
Recent studies have shown that loci outside the HLA region are involved in determining susceptibility to type 1 diabetes. Polymorphisms in the coding and noncoding regions of the genes encoding cytokines may be involved in modulating the immune response to self and nonself antigens. There is increasing evidence that an imbalance and disruption of the Thl and Th2 T cell subsets play a key role in the development of experimental and clinical type 1 diabetes. The aim of this study was to investigate the frequency of a CA dinucleotide repeat polymorphism in the interferon-gamma (IFN-gamma) gene (IFNG) and a C(-590)T polymorphism of the interleukin-4 (IL-4) gene in 236 Caucasoid patients with type 1 diabetes. There was a highly significant increase in the 3/3 IFNG genotype in the patients compared with normal healthy controls (34.3% vs. 13.5%, p<0.0001) as well as a significant increase in allele 3 of the IFNG locus in the patients compared with controls (51.9% vs. 31.7%, p<0.00001). In contrast, no significant differences were found in the frequency of the C(-590)T IL-4 polymorphism between patients and controls. These results suggest that polymorphisms of the IFNG gene may modify the function of this proinflammatory mediator and the response to pancreatic islet beta cells. 相似文献
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CA repeat allele polymorphism in the first intron of the human interferon-gamma gene is associated with lung allograft fibrosis. 总被引:5,自引:0,他引:5
M Awad V Pravica C Perrey A El Gamel N Yonan P J Sinnott I V Hutchinson 《Human immunology》1999,60(4):343-346
Interferon-gamma (IFN-gamma) is an inflammatory cytokine that has been implicated in the development of fibrosis in inflamed tissues. In this study we have analysed the association between genetically-determined high IFN-gamma production and development of fibrosis in lung transplants. The human IFN-gamma gene has a variable length CA repeat in the first intron. Our previous study showed that polymorphism of this microsatellite is associated with individual variation in the levels of IFN-gamma production. In vitro production of IFN-gamma showed significant correlation with presence of allele #2 (p < 0.01). In this study allele #2 was found to be associated with allograft fibrosis defined by transbronchial biopsy. An analysis of two groups of lung transplant recipients showed a significant increase in the frequency of allele #2 in the group which developed fibrosis after transplantation compared to the group that did not (p < 0.005). We postulate that the production of IFN-gamma, which is under genetic control, can influence the development of fibrosis in lung allografts. 相似文献
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A polymorphic CA dinucleotide repeat sequence has been identified within the promoter of the human α2(I) procollagen gene,
located at 7q21.3–q22.1. Nine alleles have been identified in unrelated individuals and the observed heterozygosity for the
polymorphism was 0.66. This marker may be useful in the prenatal diagnosis of inherited connective tissue diseases in which
the COL1A2 gene is involved. Furthermore, it may potentially improve the usefulness of the COL1A2 genetic system as an anthropogenetic marker.
Received: May 6, 1999 / Accepted: July 13, 1999 相似文献
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Association analysis of CA repeat polymorphism of the endothelial nitric oxide synthase gene with essential hypertension in Japanese 总被引:7,自引:0,他引:7
T. Nakayama M. Soma Y. Takahashi Y. Izumi K. Kanmatsuse M. Esumi 《Clinical genetics》1997,51(1):26-30
The nitric oxide synthase (NOS) gene is thought to be associated with essential hypertension (EH), because NO is implicated in endothelium-mediated vasodilation. We investigated the possible association between the alleles of simple tandem repeat DNA polymorphism of the endothelial constitutive NOS (cNOS) gene and EH in Japanese subjects. In all, 100 patients with EH and 123 subjects with normal blood pressure were studied. Polymerase chain reaction was used to amplify the CA repeat site in the endothelial cNOS gene and alleles based on the CA repeat number were determined. The allele frequencies in the hypertensive group and normotensive group were then compared. Twenty-three alleles were identified in this study of Japanese subjects. The overall distributions of allele frequencies in the two groups were not significantly different. However, comparing the allele frequencies in the EH group without left ventricular hypertrophy (LVH) and the normotensive group, the overall distributions were significantly different (p = 0.019). The 33-repeat allele was found more frequently in the EH group without LVH than in the normotensive group (p = 0.000047, Odds ratio = 3.71). In conclusion, the 33-repeat allele of the endothelial cNOS gene is associated with EH without LVH, and may be a genetic marker of EH in Japanese subjects. 相似文献
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Evidence for a functional repeat polymorphism in the promoter of the human NRAMP1 gene that correlates with autoimmune versus infectious disease susceptibility 总被引:1,自引:0,他引:1 下载免费PDF全文
A polymorphism in the promoter of human NRAMP1 encodes a Z-DNA forming dinucleotide repeat with four alleles: (1) t(gt)5ac(gt)5ac(gt)11g; (2) t(gt)5ac(gt)5 ac(gt)10g; (3) t(gt)5ac(gt) ac(gt)9g; and (4) t(gt)5ac(gt)9g. Alleles 1 and 4 are rare (gene frequencies approximately 0.001); alleles 2 and 3 occur at gene frequencies approximately 0.20-0.25 and approximately 0.75-0.80, respectively. Here, luciferase reporter gene constructs are used to show that the four alleles differ in their ability to drive gene expression. In the absence of exogenous stimuli, alleles 1, 2, and 4 are poor promoters; allele 3 drives high expression, indicating that the repeat itself has endogenous enhancer activity. All four alleles show a similar percentage enhancement of reporter gene expression in the presence of interferon-gamma, consistent with the multiple interferon-gamma response elements both 5' and 3' of the Z-DNA forming repeat. However, while the addition of bacterial lipopolysaccharide (LPS) has no effect on alleles 1 and 4, it causes significant reduction in expression driven by allele 2 and enhances expression driven by allele 3, suggesting that the juxtaposition of LPS related response elements (NFkappaB, AP-1, NF-IL6) may be differentially affected by the two commonly occurring alleles. These results are consistent with the hypothesis that chronic hyperactivation of macrophages associated with allele 3 is functionally linked to autoimmune disease susceptibility, while the poor level of NRAMP1 expression promoted by allele 2 contributes to infectious disease susceptibility. Conversely, allele 3 protects against infectious disease and allele 2 against autoimmune disease. Hence, alleles that are detrimental in relation to autoimmune disease susceptibility may be maintained in the population because they improve survival to reproductive age following infectious disease challenge. 相似文献
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In vitro cytokine production of TNFalpha and IL-13 correlates with acute liver transplant rejection.
M C Warlé A Farhan H J Metselaar W C Hop A J van der Plas M Kap S de Rave J Kwekkeboom P E Zondervan J N IJzermans H W Tilanus V Pravica I V Hutchinson G J Bouma 《Human immunology》2001,62(11):1258-1265
Individuals may differ in their capacity to produce cytokines. Since cytokines play a key role in allograft rejection, we investigated whether inter-individual differences in cytokine production by in vitro stimulated PBMC are related to the occurrence of acute liver transplant rejection. Our study group comprised 49 liver transplant recipients and 30 healthy individuals. Rejection, which occurred within one month after liver transplantation, was defined in 22 patients ("rejectors") as biopsy-proven rejection, treated with high dose prednisolone. Patients who never experienced rejection episodes were termed as "nonrejectors" (n=27). PBMC of healthy individuals and of liver transplant recipients, collected late after transplantation (mean 3.5 years), were cultured in the presence and absence of Concanavalin A. The production of TNF-alpha, IFN-gamma, IL-10, and IL-13 was measured in supernatant after 1, 2, 3, 4, and 7 days of cell culture. In cell culture, stimulated PBMC of rejectors were found to produce significantly higher levels of TNF-alpha, while there was a trend towards higher production of IFN-gamma and IL-10 as compared to nonrejectors. After grouping patients into high or low cytokine producers based upon reference levels of the healthy individuals using multivariate analysis it was found that occurrence of acute liver transplant rejection correlated to high production of TNF-alpha and low production of IL-13. After stimulated cell culture PBMC of liver transplant recipients show a differential production of TNF-alpha and IL-13 which is correlated with the occurrence of acute liver transplant rejection. 相似文献
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Transduction of renal cell carcinoma (RCC) cells in vitro with a gene for human interferon-gamma (IFN-gamma) results in enhanced expression of key molecules needed for immune recognition. In this study, we investigated the ability of soluble IFN-gamma protein to enhance expression of these key molecules. RCC cells were incubated with and without IFN-gamma, then analyzed by flow cytometry for the percent positive and mean intensity fluorescence (MIF), a measurement of mean antigen density, of HLA-I, HLA-II, ICAM-1, and tumor antigens (URO-2, URO-3, and URO-4). Results were compared to those seen for RCC cells transduced by IFN-gamma. The ability of cytotoxic T lymphocytes (CTL) to lyse RCC targets was measured using a standard [51Cr]lytic assay. Control cells were 99% (MIF 751) and 98% (MIF 315) positive for HLA-I and ICAM-1, respectively, with 2% (MIF 8) positive for HLA-II. Incubation with IFN-gamma protein resulted in 98% positive HLA-I (MIF 2288), 98% positive ICAM-1 (MIF 1132), and 95% positive HLA-II (MIF 287). The results for the cells incubated with IFN-gamma protein were similar to those for the transduced line. Importantly, the enhanced expression was maintained for several days after irradiation and cryopreservation. Expression of the URO tumor markers was not affected. Protein-treated RCC targets showed superior CTL lysis compared with untreated cells. Our results show that IFN-gamma protein incubation in vitro enhances expression of important immune recognition molecules to levels expressed by transduced cells. Increased expression may enhance tumor recognition by the host's immune system, as in the case of tumor cell vaccines. There may be no advantage to IFN-gamma transduction over in vitro incubation with IFN-gamma protein. 相似文献
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C Forsell E Enmark K Axelman M Blomberg L O Wahlund J A Gustafsson L Lannfelt 《European journal of human genetics : EJHG》2001,9(10):802-804
Several studies have shown that oestrogen treatment after menopause decreases the risk for Alzheimer's disease (AD). It is also known that oestrogen stimulates the outgrowth of nerve cells and that apolipoprotein E (Apo E) synthesis and amyloid precursor protein (APP) metabolism are regulated by oestrogen. Recently a new oestrogen receptor was identified, oestrogen receptor beta (ERbeta), located at chromosome 14q22-24. Several genes close to this chromosomal region have been implicated in AD, but the results are conflicting. Our hypothesis was that variations in the ERbeta gene could be the underlying cause to the positive findings in these genes and we have therefore investigated a CA repeat(1) in intron 5 of the ERbeta gene. Three hundred and thirty-six AD cases and 110 healthy age-matched controls were included in this study. Fourteen different alleles were found with frequencies between 0.1 and 37%. There was no significant difference between AD cases and controls when all alleles were compared. However, allele 5 was seen in 13.6% of the controls but only in 8.0% of AD cases (P=0.014; odds ratio (OR)=0.55). No AD patient homozygous for this allele was seen but three controls were homozygous. In conclusion, our findings suggest the ERbeta allele 5 to be a protective factor. However, this has to be confirmed in a larger population. 相似文献
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This study documents the production of IgE-binding factors (IgE-BFs) by unstimulated and by mitogen-activated human mononuclear cells. IgE-BFs were detected by a sensitive radioimmunoassay employing monoclonal antibodies to lymphocyte Fc epsilon R (MabER). IgE-BFs were found in the 24-hr CSN of unfractionated tonsillar lymphocytes and of their B-cell but not of their T-cell enriched fractions. When cultured for 1 week, PBMC spontaneously synthesized and released IgE-BFs in the CSN; this was significantly reduced by IgE (10 micrograms/ml). PWM, PHA and Con A significantly increased the production of IgE-BFs by PBMC, and this was not influenced by IgE. The production of IgE-BFs in response to mitogens required interactions between T and non-T cells, and IgE-BFs seemed to be derived mainly from non-T cells. However, low levels of IgE-BFs could be detected in the CSN of highly purified T cells cultured for 1 week in the presence of PHA. The production of IgE-BFs by non-T cells was T-cell dependent and it was mediated by soluble factors released from mitogen-activated T cells. T-cell factors increased the secretion of IgE-BFs by: the macrophage cell line U937, adherent cells, and adherent cell-depleted B-cell preparations. It is concluded that the majority of IgE-BFs produced by cultured human mononuclear cells are derived from B cells and monocytes, and that their production is regulated by T lymphocytes. 相似文献
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Lymphocytes from rheumatoid arthritis patients have been fused with drug-marked human myeloma cell lines and hybrids selected which secrete rheumatoid factors. Limiting dilution and soft agarose plates have been used to clone these hybrids, but so far stable clones have not been obtained. Epstein-Barr virus has been used to transform lymphocytes, and clones which secrete rheumatoid factors have been obtained. 相似文献
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Y Y Chua K Bremner N Lakdawalla J L Llobet H L Kokubu R P Orange C Collins-Williams 《The Journal of allergy and clinical immunology》1976,58(2):299-307
Sera of 86 patients clinically sensitive to foods were tested by passive sensitization of human and/or monkey lung (127 tests) and the radioallergosorbent test (RAST) (72 tests), using whole-food antigens; the results were compared with skin (prick) testing. Results of the prick test correlated with history in 76% of cases; lung sensitization correlated with history in 37% and with prick test in 57%; and RAST correlated with history in 54% and prick test in 72%. It is concluded that a very large percentage of adverse reactions to foods are IgE-mediated. The prick test is of use in diagnosis, particularly when combined with RAST; the lung sensitization test is technically impractical and not a reliable indicator. The best diagnostic method is careful history with food challenge and withdrawal and rechallenge; the latter is safe except in patients with a history of violent reaction. 相似文献
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The CSR (cellular stress response) gene encodes a protein that structurally resembles the macrophage scavenger receptor,
and is a potent regulator of intracellular reactive oxygen intermediates. We found a polymorphic dinucleotide repeat in the
first intron of the CSR gene. This polymorphism will be a useful genetic marker to study diseases associated with oxidative
stress.
Received: April 20, 1998 / Accepted: April 27, 1998 相似文献