scholarly journals Single nucleotide polymorphisms in interleukin-6 attenuates hepatocytes injury in hypoxia/re-oxygenation via STAT3 signal pathway mediated autophagy

2021 ◽  
Author(s):  
Hongwei Tang ◽  
Hongbo Fang ◽  
Wenzhi Guo ◽  
Shengli Cao ◽  
Danfeng Guo ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Signaling Pathway ◽  
Critical Role ◽  
Signal Pathway ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
L02 Cells

AbstractIschemia-reperfusion injury (IRI) is inevitable during liver surgery, and it is an important factor affecting the prognosis of patients. IL-6 rs1800796 single nucleotide polymorphisms (SNPs) can promote synthesis and secretion of IL-6 and protect hepatocytes from IRI. In this study, we investigated the mechanisms by which IL-6 alleviates hepatic IRI. We transfected lentivirus which carries IL-6 rs1800796 to L02 cells and constructed the cell line (L02-IL6) with a high expression of IL-6. The biological function of IL-6 SNPs was explored through a cell model of hypoxia-reoxygenation (H/R). Cell viability was evaluated by CCK8 and Real-Time Cell Analysis (RTCA), and found that the viability of the L02-IL6 cells was higher than that of the control group (P < 0.01). Flow cytometry assay showed that the rate of apoptosis was significantly decreased in L02-IL6 cells. Furthermore, in comparison with the control group, the level of cleaved-caspase3, which is an important marker of apoptosis, was dramatically decreased. These differences showed that the sequence variants at rs1800796 of the IL-6 gene could improve the resistance against H/R. Moreover, the levels of autophagy-related proteins, such as LC3 and Beclin-1, were upregulated in L02-IL6 group on H/R injury, which means IL-6 could alleviate apoptosis via activating the autophagy pathway. And we also found that the STAT3 signal pathway was activated. Next, we investigated whether the exogenous treatment with IL-6 affect hepatocytes and thus play a protective role. We pre-treated the L02 cells with recombinant human IL-6 for 12 h and then made H/R treatment. We found the treatment with 100 ng/ml IL-6 alleviated the damage of L02 cells and inhibited the apoptosis. And the further study revealed the pre-treatment with IL-6 activated the STAT3 signaling pathway in the L02 cells and then caused the activation of autophagy and apoptosis inhibition. IL-6 might play a critical role in alleviating hepatic IRI, through its modulation of the STAT3 signaling pathway, and activation of autophagy. Recombinant human IL-6 might be a potential therapeutic target in hepatic IRI.

The Implications of CaMK2A And MeCP2 Signalings In The Cognitive Ability of Adolescents

2021 ◽  
Author(s):  
Li-Ching Lee ◽  
Ming-Tsan Su ◽  
Hsing-Ying Huang ◽  
Ying-Chun Cho ◽  
Ting-Kuang Yeh ◽  
...  
Keyword(s):  
High School Students ◽  
Single Nucleotide Polymorphisms ◽  
Cognitive Ability ◽  
Signaling Pathway ◽  
Collective Effects ◽  
Nucleotide Polymorphisms ◽  
School Students ◽  
Single Nucleotide ◽  
Glutamatergic Signaling

Abstract The glutamatergic signaling pathway is involved in molecular learning and human cognitive ability. Specific single nucleotide polymorphisms (SNPs) in the genes encoding NMDA receptor subunits have been associated with neuropsychiatric disorders by altering glutamate transmission. But how these polymorphisms associated with cognition and brain psychological activities were rarely been explored in healthy adolescents. In this study, we screened SNPs of the glutamatergic signaling pathway to identify genetic variants associated with cognitive ability. We found that single nucleotide polymorphisms (SNPs) in subunits of ionotropic glutamate receptors, including GRIA1, GRINN1, GRIN2B, GRIN2C, GRIN3A, GRIN3B, and Calcium/ Calmodulin-dependent protein kinase II α (CaMK2A) associated with the cognitive function of students. Importantly, the plasma CaMK2A levels correlated positively with the cognitive ability of senior high school students in Taiwan. We demonstrated that the elevated CaMK2A increased its autophosphorylation at T286 and increased the expression of its downstream targets, including GRIA1 and phosphor GRIA1 in vivo. Additionally, the Methyl CpG binding protein 2 (MeCP2), a downstream target of CaMK2A, can activate the expression of CaMK2A, suggesting that MeCP2 and CaMK2A could form a positive feedback loop. In summary, we concluded that members of the glutamatergic signaling, CaMK2A, and MeCP2 were implicated in the cognitive ability of adolescents, and alternating in the CaMK2A expressing may have collective effects on the cognitive ability of youths.

scholarly journals Genotyping of Essential Hypertension Single-Nucleotide Polymorphisms by a Homogeneous PCR Method with Universal Energy Transfer Primers

2002 ◽  
Vol 48 (12) ◽  
pp. 2131-2140 ◽  
Author(s):  
Chikh Bengra ◽  
Theodore E Mifflin ◽  
Yuri Khripin ◽  
Paolo Manunta ◽  
Scott M Williams ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Single Nucleotide Polymorphisms ◽  
Restriction Endonucleases ◽  
Control Group ◽  
Italian Population ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hypertensive Patients ◽  
Unique Restriction ◽  
Set Up

Abstract Background: Human hypertension is a complex, multifactorial disease with a heritability of more than 30–50%. A genetic screening test based on analysis of multiple single-nucleotide polymorphisms (SNPs) to assess the likelihood of developing hypertension would be helpful for disease management. Methods: Tailed allele-specific primers were designed to amplify by PCR six biallelic SNP loci [three in G protein-coupled receptor kinase type 4 (GRK4): R65L, A142V, and A486V; two in angiotensinogen: −6G→A and M235T; and one in aldosterone synthase: −344C→T] associated with essential hypertension. PCRs of SNP loci were coupled (via a common sequence of 21 nucleotide tails) to incorporate Universal Amplifluor™ primers labeled with fluorescein or sulforhodamine in a homogeneous format. Use of Amplifluors in SNP PCRs produced labeled amplicons, the fluorescence of which was quantified by a microplate reader and then analyzed via an Excel macro to provide genotypes for all six SNP loci. Unique restriction endonucleases were identified for five SNP loci that could independently confirm homogeneous PCR results when needed. Results: We developed six homogeneous PCR assays that were set up, performed, and fluorometrically analyzed in 96-well microplates. Allele frequencies were determined for six SNPs in 60 Italian hypertensive patients and a control group of 60 normotensive persons. A significant correlation (P = 0.034) between one SNP [GRK4 (A486V)] and the hypertensive patients was observed. Genotyping results for five of six SNPs were confirmed by digesting corresponding amplicons with locus-specific restriction endonucleases. Conclusions: We developed a simple and homogeneous fluorescent protocol that has been used to determine the SNP genotype for six loci in a population of hypertensive and normotensive persons. We also observed a significant association (P = 0.034) between one SNP (A486V) and an Italian population of mildly hypertensive patients.

scholarly journals Association of single-nucleotide polymorphisms in the ESR2 and FSHR genes with poor ovarian response in infertile Jordanian women

2021 ◽  
Vol 48 (1) ◽  
pp. 69-79
Author(s):  
Amer Mahmoud Sindiani ◽  
Osamah Batiha ◽  
Esra’a Al-zoubi ◽  
Sara Khadrawi ◽  
Ghadeer Alsoukhni ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Statistical Significance ◽  
Ovarian Response ◽  
Control Group ◽  
P Value ◽  
Case Group ◽  
Nucleotide Polymorphisms ◽  
Poor Ovarian Response ◽  
Single Nucleotide ◽  
Number Of Patients

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART.Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing.Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively).Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.

scholarly journals Single Nucleotide Polymorphisms in IFN-γ Signaling Pathway Associated with Risk of Hepatitis B Virus Infection in Chinese Children

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yang Zhuo ◽  
Yalan Yang ◽  
Mingjun Zhang ◽  
Ying Xu ◽  
Zhongping Chen ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Single Nucleotide Polymorphisms ◽  
Signaling Pathway ◽  
Public Health Problem ◽  
Hbv Infection ◽  
Nucleotide Polymorphisms ◽  
Breakthrough Infection ◽  
Single Nucleotide ◽  
B Virus

Hepatitis B virus (HBV) infection is a challenging public health problem in China and worldwide. Mother-to-child transmission is one of the main transmission routes of HBV in highly endemic regions. However, the mechanisms of HBV perinatal transmission in children have not been clearly defined. The aim of this study was to demonstrate the association between single-nucleotide polymorphisms (SNPs) in IFN-γ signaling pathway and HBV infection or breakthrough infection in children. Two hundred and seventy-four HBV-infected children defined as test positive for hepatitis B surface antigen (HBsAg) and 353 controls defined as negative for HBsAg in China were recruited from October 2013 to May 2015. SNPs in IFN-γ signaling pathway including IFNG, IFNGR1, IFNGR2, and IL12B were genotyped. Rs2234711 in IFNGR1 was significantly associated with HBV infection in children (OR = 0.641, 95% CI: 0.450–0.913). In addition, rs2234711 was also significantly associated with HBV breakthrough infection in children born to HBsAg-positive mothers (OR = 0.452, 95% CI: 0.205–0.998). Our study confirmed that genetic variants in IFN-γ signaling pathway have significant associations with HBV infection, especially with HBV breakthrough in children. This study provides insight into HBV infection in children and could be used to help design effective strategies for reducing immunoprophylaxis failure.

scholarly journals Association Analysis of Single Nucleotide Polymorphisms in the 5′ Regulatory Region of the IL-6 Gene with Eimeria tenella Resistance in Jinghai Yellow Chickens

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 890 ◽  
Author(s):  
Hailiang Yu ◽  
Wenbin Zou ◽  
Shijie Xin ◽  
Xiaohui Wang ◽  
Changhao Mi ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Association Analysis ◽  
Direct Sequencing ◽  
Regulatory Region ◽  
Eimeria Tenella ◽  
Least Square ◽  
Bursa Of Fabricius ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Interleukin 6 (IL-6) is an immunoregulatory cytokine involved in various inflammatory and immune responses. To investigate the effects of single nucleotide polymorphisms (SNPs) and haplotypes of IL-6 on resistance to Eimeria tenella (E. tenella), SNPs in the 5′ regulatory region of IL-6 were detected with direct sequencing, and the effects of SNPs and haplotypes on resistance to E. tenella were analyzed by the least square model in Jinghai yellow chickens. Nineteen SNPs were identified in the 5′ regulation region of IL-6, among which three SNPs were newly discovered. The SNP association analysis results showed that nine of the SNPs were significantly associated with E. tenella resistance indexes; the A-483G locus was significantly associated with the GSH-Px, IL-2, and IL-17 indexes (p < 0.05); the C-447G locus was significantly associated with the SOD, GSH-Px, IL-17, and IL-2 indexes (p < 0.05); and the G-357A locus had significant effects on the CAT and IL-16 indexes (p < 0.05). Haplotype analysis showed that H2H3 and H2H5 were favorable haplotype combinations with good coccidium resistance. Furthermore, we used qRT-PCR and observed that the expression of IL-6 in the infection group was higher than that in the control group in the liver, proventriculus, small intestine, thymus, kidney, and bursa of Fabricius and extremely significantly different than that in the cecum especially (p < 0.01). In summary, SNPs and haplotypes in the 5′ regulatory region of IL-6 have important effects on E. tenella resistance, and the results will provide a reference for molecular marker selection of E. tenella resistance in Jinghai yellow chickens.

Genetic association study of SOX2 gene polymorphisms with high myopia in a Chinese population

2020 ◽  
pp. 112067212090466
Author(s):  
Lan Li ◽  
Ying Juan Cui ◽  
Yunchun Zou ◽  
Liyuan Yang ◽  
Ximin Yin ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Chinese Population ◽  
High Myopia ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Spherical Equivalent ◽  
Chi Square ◽  
Single Nucleotide ◽  
Sox2 Gene ◽  
Chi Square Test

Purpose: The aim of this study is to investigate whether SOX2 gene variants were associated with high myopia in a Chinese population. Methods: This study is conducted using case-control association analysis. This study recruited 83 healthy controls (with binocular spherical equivalent between –0.50 and +0.50 D) and 117 high myopia cases (spherical equivalent > –6.00 D in both eyes). Three single-nucleotide polymorphisms were selected from HapMap database for genotyping by direct sequencing. Statistical software (SPSS 22.0) was used for statistical analysis. The chi-square test was used to examine the difference in the frequency between cases and controls. Results: Genotype distributions in the three single-nucleotide polymorphisms were all in accordance with the Hardy–Weinberg equilibrium. The differences of rs4575941 locus genotype frequency and allele frequency between the case group and the control group were statistically significant (p = .043 and p = .029, respectively). The rs4575941 allele G frequency in the high myopia group was significantly higher than that in the control group with an odds ratio value of 1.579. However, the value of a chi-square test for the trend was 0.029, and after Bonferroni test, the p value was .087. Conclusion: In Chinese population, rs4575941 in SOX2 gene was likely to play some roles in the genetic susceptibility to high myopia; the rs4575941 allele G might be a risk gene for high myopia.

scholarly journals SINGLE-NUCLEOTIDE POLYMORPHISMS OF CALCIUM-SENSING RECEPTOR ENCODING GENE ASSOCIATED WITH CALCIUM KIDNEY STONE DISEASE IN BABYLON PROVINCE

2018 ◽  
Vol 11 (2) ◽  
pp. 417 ◽  
Author(s):  
Zahraa Isam ◽  
Rabab Omran ◽  
Ammad Hassan Mahmood
Keyword(s):  
Amino Acid ◽  
Single Nucleotide Polymorphisms ◽  
Kidney Stone ◽  
Stone Disease ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Calcium Sensing Receptor ◽  
Single Nucleotide ◽  
Kidney Stone Disease ◽  
Calcium Sensing

  Objective: The calcium-sensing receptor (CASR) is a G-protein-coupled receptor that is mainly expressed in the parathyroid and the kidneys where it regulates parathyroid hormone secretion and renal tubular calcium reabsorption. Inactivating and activating CASR gene due to mutations severally caused hypercalcemia or hypocalcemia disorders. The aim of the study was to investigate the risk factor of CASR rs1801725 (Ala986Ser) patients with renal disease.Method: The blood samples were collected from 100 patients and divided into two groups, each one containing 50 samples; chronic kidney disease and end-stage renal disease, who admitted Merjan Teaching Hospital in Babylon Province, Iraq, from February to July 2016. In addition, healthy persons as a control group (50 samples). Genotyping of CASR single-nucleotide polymorphisms (SNP) was performed using a polymerase chain reaction technique, followed by single-strand conformation polymorphism. Accordingly, these DNA polymorphisms were confirmed using DNA sequencing.Results: The conformational haplotypes of CASR, exon7 NCBI Primer3plus reference were obtained in three patterns, including two, three, and four bands, due to the presence SNPs within the studied region. These SNPs leads to change three amino acid residues of CASR, including amino acid substitutions were Ala 128→ Ser 128, Leu 155→Tye 155, and Leu 156→ Ser 156 that may affect or modified the tertiary structure of the receptor, subsequently the function like the affinity to calcium ion may be effected.Conclusion: These results suggest that the variants of CASR SNP, namely, rs1801725 might be involved in susceptibility to kidney stone disease.

scholarly journals Correlation between miRNA target site polymorphisms in the 3′ UTR of AVPR1A and the risk of hypertension in the Chinese Han population

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Liuping Zhang ◽  
Jinwei Liu ◽  
Peng Cheng ◽  
Fangchao Lv
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Mirna Target ◽  
Direct Sequencing ◽  
Chinese Han Population ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Han Population ◽  
Increased Risk

Abstract We aimed to study the relationship between rs11174811 and rs3803107 single nucleotide polymorphisms (SNPs) in miRNA target sites of the 3′ UTR in the arginine vasopressin receptor 1a gene (AVPR1A) and the risk of hypertension in the Chinese Han population. The genotypes at rs11174811 and rs3803107 were analyzed by direct sequencing in 425 Chinese Han patients with hypertension and 425 healthy subjects. AVPR1A expression was investigated by transfecting miR-526b, miR-375, and miR-186 mimics into human umbilical vein endothelial cells (HUVECs) containing AVPR1A rs11174811 CC, CA/AA and AVPR1A rs3803107 GG, GA/AA genotypes. The A alleles of rs11174811 (adjusted OR = 1.424, 95% CI: 1.231–1.599, P<0.001) and rs3803107 (adjusted OR = 1.222, 95% CI: 1.092–1.355; P=0.001) were high risk factors for hypertension. Plasma levels of miR-526b, miR-375, and miR-186 were higher in the study group than in the control group (P<0.001). The expression levels of AVPR1A mRNA in AVPR1A rs11174811 and rs3803107 mutant HUVECs were higher than those in wild-type cells (t = 8.811, 4.068 and P=0.001, 0.015, respectively). The single nucleotide polymorphisms rs11174811 and rs3803107 in the AVPR1A gene are associated with an increased risk of hypertension in the Chinese Han population. This may be related to the effect of these variants on the regulation of AVPR1A expression by miRNAs.

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