scholarly journals Single Immunoglobulin IL-1-Related Receptor (SIGIRR) Gene rs7396562 Polymorphism and Expression Level in Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Xiaoke Yang ◽  
Mingyue Zhang ◽  
Shengqian Xu ◽  
Haifeng Pan ◽  
Ruixue Leng ◽  
...  

Objectives. The aim of our study was to investigate the association of single-nucleotide polymorphism (SNP) and mRNA expression profile of single immunoglobulin IL-1-related receptor (SIGIRR) in rheumatoid arthritis (RA) in a Chinese population. Methods. SIGIRR rs7396562 polymorphism was genotyped using TaqMan allelic discrimination assay in 517 RA patients and 601 healthy controls. Simultaneously, the SIGIRR mRNA expression levels of 79 RA patients and 76 healthy controls were examined by real-time quantitative polymerase chain reaction (RT-qPCR). Results. The frequency of SIGIRR rs7396562 T allele was significantly higher in RA patients compared with healthy controls (T versus G: OR = 1.277 , 95 % CI = 1.079 − 1.511 , P = 0.004 ). The TT genotype of SIGIRR rs7396562 was more frequent in RA patients than in healthy controls ( OR = 1.547 , 95 % CI = 1.107 − 2.163 , P = 0.011 ). Moreover, we also found a significant difference in the recessive model (TT versus TG+GG: OR = 1.439 , 95 % CI = 1.122 − 1.847 , P = 0.004 ). However, no significant evidence was observed for the association of the SIGIRR rs7396562 with RA in dominant model (TT+TG versus GG: OR = 1.275 , 95 % CI = 0.947 − 1.717 , P = 0.109 ). Further analysis showed no association between SIGIRR rs7396562 polymorphism and laboratory parameters of RA patients (all P > 0.05 ). The mRNA expression of SIGIRR was decreased in PBMCs of patients with RA when compared to healthy controls ( Z = − 2.459 , P = 0.014 ). No significant differences in SIGIRR mRNA expression levels were observed in patients with RA with different genotypes ( P = 0.280 ). Conclusions. Our findings demonstrated that the dysregulation of SIGIRR might be associated with the pathogenesis of RA, and SIGIRR rs7396562 polymorphism might contribute to RA susceptibility in the Chinese population.

2021 ◽  
Author(s):  
Fengwei Cui ◽  
Shuguang Gu ◽  
Yue Gu ◽  
Jiajun Yin ◽  
Chunxia Fang ◽  
...  

Abstract Background: mTOR signaling pathway involves in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions of antipsychotic drugs, which might mediate by mTOR-dependent autophagy impairment. This study aimed to examine the mRNA expression levels of Mammalian rapamycin target protein (mTOR) pathway genes in schizophrenia patients with olanzapine treatment, which is considered to be an mTOR inhibitor and autophagy inducer. Methods: Thirty-two acute schizophrenia patients had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d), along with 32 healthy volunteers. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of schizophrenia patients, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RPTOR, and DEPTOR, were detected by real-time quantitative PCR with the fasting venous blood of all the samples. Results: The MTOR and RICTOR mRNA expression levels of acute schizophrenia patients significantly decreased than them of healthy controls, and furtherly significantly decreased after four weeks of olanzapine treatment. While DEPTOR mRNA expression levels of acute schizophrenia patients had no significant difference with them of healthy controls, but significantly increased after treatment. And the mRNA expression levels of RPTOR had no significant difference in the three groups. The pairwise correlation of MTOR, DEPTOR, RPTOR, and RICTOR mRNA expression levels in acute schizophrenia patients and healthy controls showed significant correlationships. After olanzapine treatment, the correlationships of mRNA expression levels disappeared between DEPTOR and MTOR, and also between DEPTOR and RICTOR. Conclusions: The results inferred the abnormalities of mTOR pathway, especially DEPTOR, might play important roles in autophagy mechanism of the pathophysiology in schizophrenia and olanzapine treatment.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Hu ◽  
Xiaoqian Shang ◽  
Liang Wang ◽  
Jiahui Fan ◽  
Yue Wang ◽  
...  

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.


Tumor Biology ◽  
2020 ◽  
Vol 42 (6) ◽  
pp. 101042832092452
Author(s):  
Lina Olsson ◽  
Gudrun Lindmark ◽  
Marie-Louise Hammarström ◽  
Sten Hammarström ◽  
Basel Sitohy

Objective: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker. Methods: Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I–IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase–polymerase chain reaction. Expression of migration inhibitory factor 1 protein was investigated by two-color immunohistochemistry and immunomorphometry. Results: Migration inhibitory factor 1 mRNA was expressed at 60 times higher levels in primary colon cancer tumors compared to normal colonic tissue (medians 8.2 and 0.2 mRNA copies/18S rRNA unit; p < .0001). A highly significant difference in mRNA expression levels was found between hematoxylin-eosin positive lymph nodes and hematoxylin-eosin negative lymph nodes (p < .0001). Migration inhibitory factor 1 and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer-tumor cells. Kaplan–Meier survival model and hazard ratio analysis, using a cutoff level at 2.19 mRNA copies/18S rRNA unit, revealed that patients with lymph nodes expressing high levels of migration inhibitory factor 1 mRNA had a 3.5-fold (p = .04) higher risk for recurrence, associated with a small, but significant, difference in mean survival time (7 months, p = .03) at 12 years of follow-up. Conclusion: Although migration inhibitory factor 1 mRNA expression levels were related to severity of disease and lymph node analysis revealed that colon cancer patients with high levels had a shorter survival time after surgery than those with low levels, the difference was small and probably not useful in clinical practice.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hua Jiang ◽  
Abu Moro ◽  
Yang Liu ◽  
Jiaqi Wang ◽  
Dihua Meng ◽  
...  

AbstractThe aim of this study is to investigate the expression levels of genome-wide association studies (GWAS)-identified variants near Gasdermin-C (GSDMC) and its association with lumbar disc degeneration (LDD) in a Chinese population. In accordance with previously reported findings, our study involved the top 4 variants; rs6651255, rs7833174, rs4130415, and rs7816342. A total of 800 participants, 400 LDD patients and 400 controls were involved in the study. The LDD patients were divided into two mutually exclusive subgroups: subgroup 1: lumbar disc herniation; subgroup 2: lumbar spinal stenosis. Genotyping were performed using TaqMan assay, and Enzyme-Linked Immunosorbent Assay (ELISA) used to measure the plasma GSDMC levels, while quantitative reverse-transcription (qRT)-PCR and immunohistochemistry (IHC) were used to evaluate the GSDMC expression levels. Among the studied variants, there were no statistically significant differences in allelic and genotypic frequencies between LDD patients and their controls (all P > 0.05). However, the subgroup analysis revealed a significant association between rs6651255 and rs7833174 in patients with lumbar spinal stenosis (subgroup 2). Furthermore, the max-statistic test revealed that the inheritance models of two variants of lumbar spinal stenosis were represented by the recessive model. The plasma and mRNA expression levels of GSDMC were significantly higher in patients with lumbar spinal stenosis compared with the control group (P < 0.05). Furthermore, the CC genotypes of rs6651255 and rs7833174 were significantly associated with increased plasma expression levels of GSDMC in patients with lumbar spinal stenosis (P < 0.01). Two GWAS-identified variants (rs6651255 and rs7833174) near GSDMC were associated with a predisposition to lumbar spinal stenosis. GSDMC protein and mRNA expression levels may have prognostic qualities as biomarkers for the existence, occurrence or development of lumbar spinal stenosis.


2020 ◽  
Vol 39 (9) ◽  
pp. 2611-2617
Author(s):  
Tingting Zhu ◽  
Jiaqi Hong ◽  
Zongwen Shuai ◽  
Shengqian Xu ◽  
Danfeng Qian ◽  
...  

Abstract Objective The IKBKE has been proven to be associated with systemic lupus erythematosus (SLE) in a genome-wide association study (GWAS) conducted by our group. The objective of the recent study is to investigate the contribution of IKBKE functional variants (rs2297550) to SLE. Methods We detected the regulatory effect of rs2297550 on IKBKE expression by expression quantitative trait loci (eQTL) study. Then, we investigated the differences of IKBKE mRNA expression levels in peripheral blood mononuclear cells (PBMCs) between 135 SLE patients and 130 healthy controls using quantitative real-time PCR (qRT-PCR). We further analyzed the association of SLE clinical characteristics with IKBKE mRNA expression and rs2297550 polymorphisms. Results The results of eQTL indicated the genotype “GG” of single-nucleotide polymorphism (SNP) rs2297550 was associated with lower expression levels of IKBKE (P = 0.022) in normal controls. Compared with the healthy control group, the expression levels of IKBKE mRNA in patients with SLE were significantly decreased (P = 2.32 × 10−12). In clinical characteristics, we found that IKBKE mRNA expression levels were associated with vasculitis (P = 0.015) and increased C-reactive protein (CRP) (P = 0.021) in SLE patients. Conclusion In this study, we not only detected that the variant rs2297550 of IKBKE may be closely related to SLE, but also proposed functional hypotheses for the association signals. Key Points• The rs2297550 is located in a region with transcriptional regulatory function and may regulate the expression of IKBKE via these regulatory elements.• The genotype “GG” of SNP rs2297550 was associated with lower expression levels of IKBKE.• The expression of IKBKE mRNA was decreased in SLE patients compared with healthy controls.• IKBKE contributes to the clinical characteristics of SLE.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yanchun Du ◽  
Lin Deng ◽  
Yan Li ◽  
Lu Gan ◽  
Yantang Wang ◽  
...  

Background. PERP, p53 apoptosis effector related to PMP-22, is a p53-dependent apoptosis in diverse cell types and has cell type-specific roles in p53-mediated apoptosis. However, its role in PBMCs of RA patients has remained largely unclear.Objectives. The aim of this study was to detect the expression levels of PERP on PBMCs of RA patients and healthy controls and analyze the role of PERP in the pathogenesis of RA.Methods. The mRNA expression levels of PERP and IL-17 were detected by real-time PCR in PBMCs from patients with RA (n=40) and healthy controls (n=40). The correlations of PERP expression levels to IL-17 transcripts and disease activity parameters were analyzed.Results. The PERP and IL-17 expression levels in the PBMCs were significantly decreased and increased in comparison of which in healthy controls. The mRNA expression levels of PERP in PBMCs from patients with RA were negatively correlated with IL-17 and disease activity parameters DAS28, RF, CRP, and ESR rather than Anti-CCP and ANA.Conclusions. These results demonstrated that PERP might be involved in the pathogenesis and a potential therapeutic target of RA by regulating the expression of IL-17.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13065-13065
Author(s):  
K. Uchida ◽  
K. Hayashi ◽  
H. Kuramochi ◽  
K. Kudo ◽  
S. Miyakura ◽  
...  

13065 Background: To test the hypotheses of whether the relative mRNA expression of excision cross complement-1 (ERCCI) are associated with response to CDDP+S-1 chemotherapy in recurrent colorectal cancer (CRC). We assessed the relationship between ERCC1 mRNA expression levels and the response. Methods: Thirty four patients with relapsed CRC were treated with cisplatin 30 mg/m2 on Day 1 and Day 8, and S-1 twice daily (BSA = 1.5 m2, 60 mg/day) for 21 days, followed by a 2-week period of no treatment. cDNA was derived from paraffin-embeded tumor specimens to determine ERCC1 mRNA expression relative to the internal reference gene beta-actin using fluorescence-based, real-time reverse transcriptase polymerase chain reaction (Taqman) system. Results: Among 34 CRC patients, 4 patients were evaluated as CR, 13 as PR, and 17 as NC/PD. Relative ERCC1 mRNA gene expression level showed significant difference by the response with median expression levels of 0.70/1.33/1.80 in CR/PR/NC+PD patients respectively (P = 0.04). Conclusions: These data suggest that intratumoral ERCC1 mRNA expression levels are independent predictive markers of response to CDDP+S-1 chemotherapy in colorectal cancer. No significant financial relationships to disclose.


2016 ◽  
Vol 35 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Milena Acimovic ◽  
Snezana Vidakovic ◽  
Natasa Milic ◽  
Katarina Jeremic ◽  
Milos Markovic ◽  
...  

Summary Background: The aim of this study was to investigate the role of peripheral blood markers as additional diagnostic tools to transvaginal ultrasound (TVU) findings in the diagnosis of endometriosis. Methods: This study included 40 patients undergoing laparoscopy for suspected endometriosis from January to December 2012. Preoperative levels of serum CA125, CA19-9, CEA and mRNA expression levels for survivin and VEGF were obtained. Real-time PCR was used to determine relative gene expression. A new diagnostic score was obtained by deploying the peripheral blood markers to the TVU findings. Statistical methods used were Chi-square, Fisher’s, Student’s t-test or the Mann - Whitney test. Results: There was a statistically significant difference in serum CA125, survivin and VEGF levels in patients with endometriosis and those without endometriosis (p<0.001, p=0.025 and p=0.009, respectively). False negative TVU findings were noted in 3/13 patients (23.1%) with peritoneal endometriosis without ovaries involvement. High sensitivity (93.3%), specificity (90.0%), PPV (96.6%), NPV (81.8%) and accuracy (92.5%) were obtained for a diagnostic score based on TVU and significant peripheral blood markers (CA125, survivin and VEGF). Conclusions: Determination of serum CA125, mRNA expression levels for survivin and VEGF along with TVU can contribute to higher accuracy of the noninvasive diagnostic tools for endometriosis.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Sha-Sha Tao ◽  
Yi-Lin Dan ◽  
Guo-Cui Wu ◽  
Qin Zhang ◽  
Tian-Ping Zhang ◽  
...  

Background. Recently, increasing studies have revealed that leptin is involved in the development of rheumatoid arthritis (RA). This study is aimed at exploring the association of leptin gene single nucleotide polymorphisms (SNPs) with susceptibility to RA in a Chinese population. Methods. We recruited 600 RA patients and 600 healthy controls from a Chinese population and analyzed their three leptin SNPs (rs10244329, rs2071045, and rs2167270) using the improved Multiplex Ligase Detection Reaction (iMLDR) assays. The associations of these SNPs with clinical manifestations of RA were also analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed for plasma leptin determination. Results. No significant difference in either allele or genotype frequencies of these three SNPs between RA patients and healthy controls was observed (all P > 0.05 ). Association between the genotype effects of dominant, recessive models was also not found (all P > 0.05 ). No significant difference in plasma leptin levels was detected between RA patients and controls ( P > 0.05 ). Conclusion. Leptin gene (rs10244329, rs2071045, and rs2167270) polymorphisms are not associated with RA genetic susceptibility and its clinical features in the Chinese population.


2020 ◽  
Vol 48 (5) ◽  
pp. 030006052091841
Author(s):  
Lixing Chen ◽  
Zengyu Yao ◽  
Shanshan Qu ◽  
Jialing Zhang ◽  
Jiping Zhang ◽  
...  

Objectives To investigate the antidepressant effects of electroacupuncture (EA) on chronic unpredictable mild stress (CUMS) in rats, as well as the effects of EA on hippocampal neurons, synaptic morphology, and 5-hydroxytryptamine (HT) receptor expression. Methods Forty adult male Wistar rats were randomly divided into normal control, CUMS, EA, and paroxetine groups. CUMS modeling was performed for 21 days, followed by 14 days of intervention: rats in the EA group underwent stimulation of GV20 and GV29 acupuncture points for 30 minutes daily; rats in the paroxetine group were administered paroxetine daily. Behavioral tests, transmission electron microscopy, western blotting, and real-time quantitative polymerase chain reaction were used to evaluate the effects of the intervention. Results EA treatment reversed the behavioral changes observed in rats due to CUMS modeling; it also improved the pathological changes in organelles and synaptic structures of hippocampal neurons, and upregulated the protein and mRNA expression levels of 5-HT1A receptor. There were no significant differences in 5-HT1B receptor protein and mRNA expression levels among the groups. Conclusions EA treatment can alleviate depression-like symptoms in CUMS rats. The underlying mechanism may include promoting the expression of 5-HT1A receptor mRNA and protein, thereby improving synaptic plasticity in the hippocampus.


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