scholarly journals ITM2A Expands Evidence for Genetic and Environmental Interaction in Graves Disease Pathogenesis

2016 ◽  
Vol 102 (2) ◽  
pp. 652-660 ◽  
Author(s):  
Xiao-Ping Ye ◽  
Fei-Fei Yuan ◽  
Le-Le Zhang ◽  
Yu-Ru Ma ◽  
Man-Man Zhang ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Genetic Predisposition ◽  
Bacterial Infections ◽  
Mononuclear Cells ◽  
Susceptibility Gene ◽  
Interferon Γ ◽  
Graves Disease ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Peripheral Blood Mononuclear

Abstract Context: Graves disease (GD) is a common autoimmune disease triggered by genetic predisposition and environmental factors. However, the mechanisms of interaction between genetic and environmental factors contributing to the development of GD remain unknown. Objective: We aimed to identify GD susceptibility variants and genes on Xq21.1 locus and interpret the contribution of interaction between genetic predisposition on Xq21.1 and environmental factors to GD. Design: We performed refining study on Xq21.1 in a 2-stage study and carried out expression quantitative trait locus analysis of the best association signal with GD. Setting and Participants: A total of 4316 GD patients and 4374 sex-matched controls were collected from the Chinese Han population by cooperation with multiple hospitals. Results: We identified that rs3827440 or its linkage single nucleotide polymorphisms (SNPs) were probably the causal variant in the Xq21.1 locus, with the most substantial association with GD in our combined cohorts (P = 2.45 × 10−15). The genotypes of rs3827440 were correlated with the expression of ITM2A in monocytes and peripheral blood mononuclear cells (PBMCs) from healthy volunteers. Notably, the expression of ITM2A in monocytes after lipopolysaccharide (LPS) and interferon-γ (INF-γ) stimulation showed substantial difference among the volunteers that carried different genotypes of rs3827440 (P = 9.40 × 10−7 and P = 1.26 × 10−5 for 24 hours’ LPS and INF-γ stimulation, respectively). Moreover, ITM2A expression was significantly decreased in PBMCs from untreated GD patients than that from controls. Conclusion: The results suggest that ITM2A might be a susceptibility gene for GD in the Xq21.1 locus, and environmental factors, such as viral and bacterial infections, probably contribute to GD pathogenesis by interacting with the risk SNP rs3827440 mediating the regulation of ITM2A expression.

Genetic variations in the SOCS3 gene in patients with Graves’ ophthalmopathy

2015 ◽  
Vol 68 (6) ◽  
pp. 448-452 ◽  
Author(s):  
Ruijia Yan ◽  
Junjie Yang ◽  
Ping Jiang ◽  
Ling Jin ◽  
Jing Ma ◽  
...  
Keyword(s):  
Western Blot ◽  
Mononuclear Cells ◽  
Pcr Analysis ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Qrt Pcr ◽  
Graves Ophthalmopathy ◽  
Socs3 Mrna

AimsTo explore the role of the suppressor of cytokine signalling 3 (SOCS3) gene in Graves’ ophthalmopathy (GO) patients.MethodsA case–control study was conducted in a Chinese Han population by recruiting 114 Graves’ disease (GD) patients with GO and 156 GD patients without GO. We determined SOCS3 mRNA and protein levels in Epstein–Barr virus-transformed lymphoblastoid cell lines (EBV-LCLs) from peripheral blood mononuclear cells (PBMCs) by quantitative real-time (QRT)-PCR analysis and western blot analysis. We also genotyped five single nucleotide polymorphisms (SNPs) in the SOCS3 locus (SOCS3 rs12952093, rs4969170, rs4969168, rs4969169 and rs2280148) in all 270 GD patients using ligase detection reaction and multiplex PCR analyses. QRT-PCR and western blot assays were then performed to compare SOCS3 mRNA and protein levels between the rs4969170 AA and GG genotype groups from 20 GO patients.ResultsBasal SOCS3 mRNA and protein expression levels were significantly increased in patients with GO (p<0.05). The SOCS3 rs4969170 AA genotype was strongly associated with GO (OR=3.5, 95% CI 1.6 to 7.5, p=0.001). The AA genotype carriers had significantly higher SOCS3 mRNA and protein levels than those with the GG genotype (p<0.05).ConclusionsPatients with GD who carry the AA genotype of the rs4969170 SNP in SOCS3 are more susceptible to the development of GO.

scholarly journals Expression Profiling of Transcriptome and Its Associated Disease Risk in Yang Deficiency Constitution of Healthy Subjects

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ruoxi Yu ◽  
Yin Yang ◽  
Yuanyuan Han ◽  
Pengwei Hou ◽  
Yingshuai Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Clinical Medicine ◽  
Disease Risk ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Evidence ◽  
Chinese Han ◽  
Peripheral Blood Mononuclear

Objectives. Differences among healthy subjects and associated disease risks are of substantial interest in clinical medicine. According to the theory of “constitution-disease correlation” in traditional Chinese medicine, we try to find out if there is any connection between intolerance of cold in Yang deficiency constitution and molecular evidence and if there is any gene expression basis in specific disorders. Methods. Peripheral blood mononuclear cells were collected from Chinese Han individuals with Yang deficiency constitution (n=20) and balanced constitution (n=8) (aged 18–28) and global gene expression profiles were determined between them using the Affymetrix HG-U133 Plus 2.0 array. Results. The results showed that when the fold change was ≥1.2 and q ≤ 0.05, 909 genes were upregulated in the Yang deficiency constitution, while 1189 genes were downregulated. According to our research differential genes found in Yang deficiency constitution were usually related to lower immunity, metabolic disorders, and cancer tendency. Conclusion. Gene expression disturbance exists in Yang deficiency constitution, which corresponds to the concept of constitution and gene classification. It also suggests people with Yang deficiency constitution are susceptible to autoimmune diseases, enteritis, arthritis, metabolism disorders, and cancer, which provides molecular evidence for the theory of “constitution-disease correlation.”

scholarly journals Gene–gene and gene-environment interactions on cord blood total IgE in Chinese Han children

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Li Hua ◽  
Quanhua Liu ◽  
Jing Li ◽  
Xianbo Zuo ◽  
Qian Chen ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Cord Blood ◽  
Synergistic Effects ◽  
Gene Interaction ◽  
Independent Effect ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Gene Environment Interaction ◽  
Gene Environment

Abstract Background IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population. Methods 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods. Results A four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2). Conclusions Gene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.

Toll like receptor 9 (TLR 9) expression in peripheral blood mononuclear cell (PBMCs) from treated and untreated Grave’s disease patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Ashraf M Okba ◽  
Rasha Y Shaheen ◽  
Gehan M. H Mostafa ◽  
Hanan M Ali ◽  
Sylvia W Abo El Fadle ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cell ◽  
Mononuclear Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Lymphocytes ◽  
Graves Disease ◽  
Toll Like Receptor ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Abstract Background It is well known that Autoimmune thyroid disease is multifactorial with multiple genetic and environmental factors, immune malfunction also incriminated in the development of this disease, The exact pathogenesis of this disease remains unclear despite the fact that the production of autoantibodies destroys self-tolerance and agitate the adaptive immune system. Our study will answer the question is there a difference in Toll like receptor 9 (TLR 9) expression in peripheral blood mononuclear cell (PBMCs) from Grave’s disease patients. Objective to measure TLR9 percentage expression on peripheral blood mononuclear cells in patients with Graves’ disease. Methods 60 subjects were included in this study; 30 with Graves’ disease and 30 healthy individuals as control group. All the patients were subjected to the following: Full history, clinical examination, thyroid functions, Thyroid ultrasound, Radioisotope thyroid scan: to assess uptake of thyroid gland and Toll like receptor 9 (TLR 9) percentage expression on peripheral blood mononuclear cells will be analyzed using flow cytometry technique. Results The present study proved that patients with Graves’ disease had higher levels of percentage expression of TLR 9 on peripheral blood lymphocytes. Conclusion percentage expression of TLR9 on peripheral blood lymphocytes is higher in Graves’ patients.

scholarly journals Hemodialysis-Related Lymphomononuclear Release of Interleukin-12 in Patients with End-Stage Renal Disease

1999 ◽  
Vol 10 (10) ◽  
pp. 2171-2176 ◽  
Author(s):  
BRUNO MEMOLI ◽  
LUIGI MARZANO ◽  
VINCENZO BISESTI ◽  
MICHELE ANDREUCCI ◽  
BRUNA GUIDA
Keyword(s):  
Mononuclear Cells ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Mitogen Stimulation ◽  
Ifn Γ ◽  
Uremic Patients ◽  
Stage Renal Disease ◽  
End Stage

Abstract. Interleukin-12 (IL-12) is a cytokine produced by peripheral blood mononuclear cells (PBMC) that causes interferon-γ (IFN-γ) production and enhancement of cell-mediated cytotoxicity. To clarify the role of hemodialysis biocompatibility on IL-12 production and uremic immunodeficiency, we have studied the IL-12 and IFN-γ release by PBMC harvested from 12 patients dialyzed with cuprophan membrane (CU), eight patients dialyzed with polymethylmethacrylate membrane (PMMA), and eight nondialyzed uremic patients (UR). Ten healthy subjects constituted the control group (CON). PBMC were cultured for 48 h with and without nonspecific mitogen stimulation. In unstimulated conditions, CU showed an IL-12 PBMC production higher than CON, UR, and PMMA (46.67 ± 30.13versus2.56 ± 1.38, 6.16 ± 7.09, and 4.62 ± 4.76 pg/ml, respectively;P< 0.01). IL-12 production was correlated with C3a concentration measured at the outlet of hemodialyzer after 15 min of dialysis (r= 0.69,P< 0.01). IL-12 release in CU remained unchanged under mitogen stimulation (44.34 ± 23.86 pg/ml) and was lower than in CON, UR, and PMMA (66.0 ± 12.41, 68.37 ± 25.78, and 67.75 ± 22.61 pg/ml, respectively;P< 0.05). IFN-γ production was similar, in unstimulated conditions, in all groups. Under stimulation, IFN-γ release was lower in CU (13.42 ± 12.04 IU/ml) than in CON, UR, and PMMA (51.84 ± 30.74, 32.16 ± 13.86, and 32.16 ± 13.86 IU/ml, respectively;P< 0.01). These results demonstrate that hemodialysis with CU induces monocyte activation with an enhanced release of IL-12. On the contrary, stimulated PBMC production of both IL-12 and IFN-γ is lower in these patients than in CON, UR, and PMMA. The altered release of these cytokines could play a role in cell-mediated immunodeficiency of the uremic patients dialyzed with CU.

scholarly journals Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 643-649 ◽  
Author(s):  
M Carol ◽  
A Lambrechts ◽  
A Van Gossum ◽  
M Libin ◽  
M Goldman ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Gastrointestinal Diseases ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

Sign in / Sign up

Export Citation Format

Share Document