scholarly journals Association of the Adipokines Chemerin, Apelin, Vaspin and Omentin and Their Functional Genetic Variants with Rheumatoid Arthritis

2021 ◽  
Vol 11 (10) ◽  
pp. 976
Author(s):  
Alaa S. Wahba ◽  
Maha E. Ibrahim ◽  
Dina M. Abo-elmatty ◽  
Eman T. Mehanna

Adipokines were shown to exert crucial roles in rheumatic diseases. This study aimed to assess the role of chemerin, apelin, vaspin, and omentin adipokines and their genetic variants rs17173608, rs2235306, rs2236242, and rs2274907, respectively, in rheumatoid arthritis (RA) pathogenesis in Egyptian patients. A total of 150 RA patients and 150 healthy individuals were recruited. Blood samples were collected and used for genotyping. Serum was separated and used for expression analysis by quantitative PCR, and various biochemical markers determination by ELISA. Serum protein levels of chemerin and vaspin, as well as their gene expression levels were higher, while those of apelin and omentin were lower in RA patients and were associated with most of RA clinical and laboratory characteristics. G allele of chemerin rs17173608, T allele of vaspin rs2236242, and T allele of omentin rs2274907 were more frequent in RA patients. Serum levels and gene expression levels of chemerin in GG genotype carriers and vaspin in TT genotype group were significantly higher, while those of omentin in TT genotype carriers were significantly lower than RA patients with other genotypes. There was no association between apelin rs2235306 and RA. Chemerin rs17173608, vaspin rs2236242, and omentin rs2274907 polymorphisms were associated with increased susceptibility to RA.

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 355 ◽  
Author(s):  
Agnieszka Paradowska-Gorycka ◽  
Barbara Stypinska ◽  
Andrzej Pawlik ◽  
Damian Malinowski ◽  
Katarzyna Romanowska-Prochnicka ◽  
...  

We investigated kinase insert domain-containing receptor (KDR) polymorphisms and protein levels in relation to susceptibility to and severity of Rheumatoid Arthritis (RA). 641 RA patients and 340 controls (HC) were examined for the rs1870377 KDR variant by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method and for rs2305948 and rs2071559 KDR single nucleotide polymorphisms (SNPs) by TaqMan SNP genotyping assay. KDR serum levels were determined by enzyme-linked immunosorbent assay (ELISA). The rs1870377 KDR variant has shown association with RA under the codominant (p = 0.02, OR = 1.76, 95% CI = 1.09–2.85) and recessive models (p = 0.019, OR = 1.53, 95% CI = 1.07–2.20). KDR rs2305948 was associated with RA under the dominant model (p = 0.005, OR = 1.38, 95% CI = 1.10–1.73). Under the codominant model, the frequency of the rs2071559 TC and GG genotypes were lower in RA patients than in controls (p < 0.001, OR = 0.51, 95% CI = 0.37–0.69, and p = 0.002, OR = 0.57, 95% CI = 0.39–0.81). KDR rs2071559 T and rs2305948 A alleles were associated with RA (p = 0.001, OR = 0.60, 95% CI = 0.45–0.81 and p = 0.008, OR = 1.71, CI = 1.15–2.54). KDR rs2305948SNP was associated with Disease Activity Score (DAS)-28 score (p < 0.001), Visual Analog Scale (VAS) score (p < 0.001), number of swollen joints (p < 0.001), mean value of CRP (p < 0.001). A higher KDR serum level was found in RA patients than in HC (8018 pg/mL versus 7381 pg/mL, p = 0.002). Present results shed light on the role of KDR genetic variants in the severity of RA.


2020 ◽  
Vol 24 (3) ◽  
Author(s):  
Nazila Payandeh ◽  
Maghsoud Peeri ◽  
Mohammad Ali Azarbayjani ◽  
Seyed Ali Hosseini

Background: A healthy lifestyle, nutrition, and exercise can improve bone mass via several mechanisms. Objectives: This study assessed the effects of four weeks of palm pollen consumption along with resistance training on protein and gene expression levels of Runt-related transcription factor 2 (Runx2) in bone tissue of rats. Methods: Thirty-six rats were selected and assigned into six groups, including (1) training + testosterone, (2) training + palm pollen, (3) testosterone, (4) palm pollen, (5) training and (6) sham. Then, 100 mg/kg of palm pollen was prescribed five days per week. Resistance training was performed five sessions per week, and 2 mg/kg of testosterone propionate was prescribed peritoneally. Gene expression and protein levels of Runx2 were measured via the real-time PCR and Western blot methods. Results: Training had a significant effect on the increase in Runx2 protein levels (P ≤ 0.05). Training + testosterone, training + palm pollen, testosterone, and palm pollen had significant effects on gene expression and protein levels of Runx2 (P ≤ 0.05). Training + testosterone and training + palm pollen had more favorable effects on the increase of gene expression and protein levels of Runx2 than had testosterone, palm pollen, and training (P ≤ 0.05). Conclusions: Although training, palm pollen, and testosterone alone could increase the Runx2 protein levels in the bone tissue of rats, training with palm pollen and training with testosterone appeared to have more favorable effects on the increase of gene expression and protein levels of Runx2 than either alone.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3977-3977
Author(s):  
Ida Bruun Kristensen ◽  
Jacob Haaber ◽  
Maria B Lyng ◽  
Lise Pedersen ◽  
Lars Melholt Rasmussen ◽  
...  

Abstract Abstract 3977 Osteolytic bone disease (OBD) in multiple myeloma (MM) is known to be caused by a combination of osteoclast hyperactivation and osteoblast inhibition. One of the pathways known to be involved in osteoblast inhibition from in vitro studies is the HGF pathway consisting of HGF, its receptor MET, the co-receptor Syndecan-1 (SDC-1), the partial MET antagonist Decorin and HGF activator responsible for HGF processing to its active form. So far, gene expression studies in MM have been performed on isolated MM plasma cells or bone marrow (BM) aspirates, which are not completely representative of the cell composition in the BM micro-environment. We used a novel strategy, whereby gene expression of factors associated with the HGF pathway was evaluated in snap-frozen BM biopsies, and moreover we determined the protein levels in matched BM plasma samples. An additional BM core biopsy obtained during the diagnostic procedure of MM patients was snap-frozen. Biopsies were cut, homogenized and RNA was purified and analyzed by qRT-PCR using low density arrays (Applied Biosystems). The relative quantitative gene expression was calculated using 3 internal reference genes (ABL, GAPDH and GUS). OBD was evaluated using standard radiographs. All patients were untreated and did not receive medicine that could influence bone remodeling. We examined 10 healthy volunteers (HV), 35 monoclonal gammopathy of unknown significance (MGUS) and 65 untreated MM patients, which according to radiographic findings were divided into NO/LOW and advanced OBD, i.e. OBD in ≥2 regions. ELISA was performed on a total of 31 matched BM plasma samples of HV, MGUS and MM obtained at the same time point as the biopsies. In addition, extra samples without gene data (N=52) were analyzed. Commercial kits for SDC-1 (Diaclone), HGF (RnD, Quantikine) and Decorin (RnD, Duoset) were run in duplicates according to manufacturer's instructions. Gene expression of HGF, SDC1, and MET were significantly different comparing HV, MGUS, no/low and advanced OBD (p<0.05) (For HGF, see figure 1). Decorin was not associated to OBD. HGF activator was not expressed in any of our samples, but only in the positive control. A significant correlation between gene and protein expression levels measured by ELISA was found for SDC-1 (Spearman's rho= 0.463, p=0.0058) and HGF (Spearman's rho=0.45, p=0.01). No correlation was found between Decorin gene levels and BM plasma levels (Spearman's rho =-0.24, p=0.22). The protein level of SDC-1 and HGF in BM plasma were both upregulated in MM and associated significantly to OBD level (p<0.05), while Decorin were significantly downregulated in MGUS and MM samples compared to HVs (p<0.05). A significant difference in HGF BM plasma levels were found between patients with no/limited OBD (median: 1.7ng/mL) and advanced OBD (median: 6.2ng/mL) in BM plasma. In our expression study reflecting the in vivo situation in MM patients, genes in the HGF pathway and proteins were significantly associated to OBD. The use of whole snap-frozen BM biopsies is a novel strategy for evaluation of gene expression in MM making it possible to investigate patients independent of degree of MM plasma cell infiltration. In addition to the dys-regulated gene expression levels alteration of SDC-1 and HGF was also observed at protein level, supporting the gene expression findings, and underscoring the usefulness of BM biopsies for gene expression studies in MM. Furthermore, our study for the first time shows up regulation of HGF in association with OBD at both gene and protein level in a large clinical material. Figure 1A. HGF Gene Expression levels in whole snap-frozen BM biopsies. Figure 1B. HGF protein levels in BM plasma (pg/mL). 1 = HV, 2 = MGUS, 3 = no/low OBD MM, 4 = advanced OBD MM. Figure 1A. HGF Gene Expression levels in whole snap-frozen BM biopsies. Figure 1B. HGF protein levels in BM plasma (pg/mL). 1 = HV, 2 = MGUS, 3 = no/low OBD MM, 4 = advanced OBD MM. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Author(s):  
Jian-Rong Li ◽  
Mabel Tang ◽  
Yafang Li ◽  
Christopher I Amos ◽  
Chao Cheng

Abstract Background: Expression quantitative trait loci (eQTLs) analyses have been widely used to identify genetic variants associated with gene expression levels to understand what molecular mechanisms underlie genetic traits. The resultant eQTLs might affect the expression of associated genes through transcriptional or post-transcriptional regulation. In this study, we attempt to distinguish these two types of regulation by identifying genetic variants associated with mRNA stability of genes (stQTLs).Results: Here, we presented a computational framework that take the advantage of recently developed methods to infer the mRNA stability of genes based on RNA-seq data and performed association analysis to identify stQTLs. Using the Genotype-Tissue Expression (GTEx) lung RNA-Seq data, we identified a total of 142,801 stQTLs for 3,942 genes and 186,132 eQTLs for 4,751 genes from 15,122,700 genetic variants for 13,476 genes, respectively. Interesting, our results indicated that stQTLs were enriched in the CDS and 3’UTR regions, while eQTLs are enriched in the CDS, 3’UTR, 5’UTR, and upstream regions. We also found that stQTLs are more likely than eQTLs to overlap with RNA binding protein (RBP) and microRNA (miRNA) binding sites. Our analyses demonstrate that simultaneous identification of stQTLs and eQTLs can provide more mechanistic insight on the association between genetic variants and gene expression levels.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 190-190
Author(s):  
Francesca Battaglin ◽  
Yi Xiao ◽  
Joshua Millstein ◽  
Andreas Seeber ◽  
Hiroyuki Arai ◽  
...  

190 Background: Wnt signaling deregulation is a primary driver of colorectal carcinogenesis. RNF43 is a key suppressor of Wnt activation while R-Spodin inhibits RNF43 activity. RNF43 mutations are associated with the serrated neoplasia pathway, BRAF mutation and MSI. We hypothesized that genetic variants in the R-Spodin/RNF43 complex and corresponding genes expression levels may predict cetuximab efficacy in mCRC pts. Methods: Genomic DNA from blood samples of pts enrolled in the randomized FIRE-3 trial was genotyped through the OncoArray, a custom array manufactured by Illumina. The impact on outcome of 17 functional SNPs within RNF43/ ZNRF3, LGR4/5 and RSPO1/2/3 was analyzed in 129 pts treated with first-line FOLFIRI/cet and 107 pts treated with FOLFIRI/bevacizumab (bev). Gene expression levels were measured from tumor tissue samples from 102 pts in the cet arm by HTG EdgeSeq Oncology Biomarker Panel. False discovery rate (FDR) for gene expression analysis was computed using the Benjamini-Hochberg approach (significant Q < 0.1). Results: In the cet cohort, pts with the C/C genotype of ZNRF3 rs132531 had significantly shorter overall survival compared to any T allele carriers (mOS: 20.3 vs 52 mo) in both univariable (HR 3.61, 95% CI 1.65-7.88, P < .001) and multivariable analysis (adjusted P = .01). Conversely, RSPO1 rs4652964 any G allele carriers showed increased tumor response (TR) rates compared to the A/A genotype (83 vs 66 %, P = .04). These associations were not observed in bev arm. Lower gene expression levels of RNF43 were associated with shorter PFS in pts with right-sided tumors receiving FOLFIRI/cet ( P = .006, Q < 0.1). RSPO1 expression levels were also associated with TR in the same subgroup (70 vs 10% in high vs low; P = .001, Q < .05). RNF43 expression was associated with TR in pts with left-sided tumors (82% in high vs 58% in low, P = .014, Q = 0.1). Conclusions: Our results provide the first evidence that germline polymorphisms and tumor gene expression levels of RNF43/ ZNRF3 and RSPO1 may have a predictive value in mCRC pts receiving first-line cetuximab-based treatment and contribute to modulate anti-EGFRs activity.


Genome ◽  
2011 ◽  
Vol 54 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Jenna L. Woody ◽  
Andrew J. Severin ◽  
Yung-Tsi Bolon ◽  
Bindu Joseph ◽  
Brian W. Diers ◽  
...  

Studies have indicated that exon and intron size and intergenic distance are correlated with gene expression levels and expression breadth. Previous reports on these correlations in plants and animals have been conflicting. In this study, next-generation sequence data, which has been shown to be more sensitive than previous expression profiling technologies, were generated and analyzed from 14 tissues. Our results revealed a novel dichotomy. At the low expression level, an increase in expression breadth correlated with an increase in transcript size because of an increase in the number of exons and introns. No significant changes in intron or exon sizes were noted. Conversely, genes expressed at the intermediate to high expression levels displayed a decrease in transcript size as their expression breadth increased. This was due to smaller exons, with no significant change in the number of exons. Taking advantage of the known gene space of soybean, we evaluated the positioning of genes and found significant clustering of similarly expressed genes. Identifying the correlations between the physical parameters of individual genes could lead to uncovering the role of regulation owing to nucleotide composition, which might have potential impacts in discerning the role of the noncoding regions.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Marwa S. Abdel-Tawab ◽  
Hanan H. Fouad ◽  
Dalia A. Omran ◽  
Aml E. Abdou ◽  
Shaimaa Mohamed Zaied ◽  
...  

Background. Hepatitis C virus (HCV) is considered a major global public health problem. Recently, there are great advances in HCV therapy, but there are some limitations that are creating an urgent need for assessment of some cytokines that have a potent antiviral effect in the immune system and anti-inflammatory effects to provide a potential novel immunotherapeutic target in HCV infection. Objective. This study was directed to assess the serum levels and gene expression levels of Galectin-4 (LEG4), Interleukin-27 (IL-27), and Complement-7 (C-7) and their correlation with the viral load in HCV infection. Subjects and Methods. This work was conducted on 80 subjects, Group 1 ( n = 40 ) early detected HCV patients and Group 2 ( n = 40 ) healthy controls. LEG4, IL-27, and C-7 were assessed at the protein levels by ELISA, and their gene expression was assessed by RT-qPCR. The viral load was measured by PCR. Results. There were significant elevations in the mean levels of gene expression and serum levels of all studied parameters LEG4, IL-27, and C-7 in the HCV group compared to the control group. Significant negative correlations between the viral load and each of the serum proteins and gene expressions of both LEG4 and IL-27 in HCV patients were found. The gene expression levels of LEG4, IL-27, and C-7 were positively correlated with their corresponding serum proteins in HCV patients.Conclusion. LEG4 and IL-27 showed significant negative correlations with the viral load, which could be an immune response to the control of the extent of hepatic inflammation, thus creating a potential novel immunotherapeutic approach in HCV infection for further studies or therapeutic clinical trials.


2013 ◽  
Vol 35 (1) ◽  
pp. 9-13
Author(s):  
Zehra Dilşad Çoban ◽  
Deniz Torun ◽  
Ferit Avcu ◽  
Ali Uğur Ural ◽  
Erhan Parıltay ◽  
...  

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Zahra Giti ◽  
Abdolali Banaeifar ◽  
Sajad Arshadi ◽  
Mohammad Ali Azarbayjani

Background: Alzheimer’s disease (AD) is a common disease in the elderly that is associated with impaired metabolism and biology of the hippocampus. Although the role of exercise and natural antioxidants in improving the disease has been reported, the role of muscle contraction-related physical activity along with royal jelly (RJ) consumption is not yet well understood. Objectives: This study aimed to investigate the effect of eight weeks of training on positive slope (ETPS) and negative slope (ETNS) with royal jelly (RJ) consumption on O-6-methylguanine DNA methyltransferase (MGMT) and ATPase gene expression levels in the hippocampus tissue of trimethyltin (TMT)-induced AD rats. Methods: In this experimental trial, 36 male Sprague-Dawley AD rats (induced with 8 mg/kg TMT) were divided into (1) control + normal saline/royal jelly solvent) (Sh); (2) ETPS; (3) ETNS; (4) ETPS + RJ; (5) ETNS + RJ, and (6) RJ groups. Six rats were placed in the healthy control (HC) group. Then the training groups trained on ( + 15 and -15) slopes for eight weeks, five sessions per week, and each session lasted 60 minutes at a speed of 16 m/min. The royal jelly (RJ) groups received 100 mg/kg royal jelly per day by intraperitoneal injection. Results: ETNS, ETPS, ETPS + RJ, and ETNS + RJ increased MGMT gene expression (P ≥ 0.05). ETPS and ETPS + RJ also increased ATPase gene expression (P ≥ 0.05). However, RJ had no significant effect on increasing MGMT and ATPase gene expression in the hippocampus tissue of AD rats (P ≥ 0.05). Conclusions: It seems that the improvement of DNA damage markers and energy levels depends on the type of contraction. Although training on positive and negative slopes with royal jelly consumption has an interactive effect on DNA repair markers, training on a positive slope and royal jelly consumption has an interactive effect on ATPase gene expression.


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