Occurrence of Interleukin-2 (330 G/T) Promoter Polymorphism in ARV associated hepatotoxicity

2019 ◽  
Vol 19 (3) ◽  
pp. 206-215
Author(s):  
HariOm Singh ◽  
Nayana Nambiar ◽  
Dharmesh Samani ◽  
Raman R. Gangakhedkar
Keyword(s):  
Hepatic Injury ◽  
Interleukin 2 ◽  
Promoter Polymorphism ◽  
Healthy Controls ◽  
Hiv Replication ◽  
Hiv Patients ◽  
Pcr Rflp

Background: IL-2 cytokine is involved in HIV replication and is also known to cause hepatic injury. Polymorphisms in the IL-2 gene are associated with altered interleukin-2 production. Methods: Hence, we assessed the prevalence of IL-2-303G/T polymorphism in 165 HIV patients (34 with and 131without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method. Results: In patients with hepatotoxicity, IL-2-303GT, -303GT+TT genotypes were less prevalent as compared to without hepatotoxicity and healthy controls (29.4% vs. 42.7%, 58.8% vs. 69.5%; 29.4% vs. 40.6%, 58.8% vs. 66.5%, respectively). In patients with hepatotoxicity using tobacco and alcohol, IL-2-303GT,-303TT genotypes were distributed higher as compared to non-users (42.9% vs. 25.9%, OR=8.52, 42.9% vs. 25.9%, OR=9.09, and 28.6% vs. 29.6%, OR=1.63, 42.9% vs. 25.9%, OR=2.93), while IL-2-303TT genotype occurred more often in HIV patients consuming alcohol (34.1% vs. 23.0%). Nevirapine users with hepatotoxicity overrepresented the IL-2-303GT,-303TT genotypes as compared to efavirenz (34.8% vs. 18.2%, OR=4.64, 34.8% vs. 18.2%, OR=3.88). Among nevirapine users, IL-2-303GT genotype was associated with susceptibility to the acquisition of hepatotoxicity with borderline significance (OR=4.24, P=0.06). HIV patients using nevirapine majorly represented the IL-2-303TT genotype (26.9% vs. 25.0%, OR=2.35) while HIV patients with nevirapine + alcohol usage presented the IL-2 -330TT genotype at a higher frequency (34.2% vs. 23.5%, OR=1.51). In patients with hepatotoxicity using nevirapine + alcohol, the genotype IL-2 - 330TT was predominant (60.0% vs. 27.8%, OR=3.16). Conclusion: Thus, IL-2-303G/T polymorphism did not confer the susceptibility to ARV associated hepatotoxicity. However, IL-2-303G/T polymorphism with nevirapine usage may facilitate the risk for acquisition of ARV associated hepatotoxicity.

scholarly journals IL-1RN and IL-1βPolymorphism and ARV-Associated Hepatotoxicity

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
HariOm Singh ◽  
Dharmesh Samani ◽  
Vijay Nema ◽  
Manisha V. Ghate ◽  
R. R. Gangakhedkar
Keyword(s):  
Hepatic Injury ◽  
Healthy Controls ◽  
Severe Hepatotoxicity ◽  
Pcr Rflp ◽  
Alcohol Users

The severity of hepatic injury depends upon cytokines. Previous studies associatedIL-1RNallele 2 withIL-1βproduction. Hence, we examined the association ofIL-1 RNandIL-1βpolymorphisms with ARV-associated hepatotoxicity. Genotyping ofIL-1RN(VNTR),IL-1β(-511C/T) polymorphisms was done in 162 HIV-infected patients, 34 with ARV hepatotoxicity, 128 without hepatotoxicity, and 152 healthy controls using PCR and PCR-RFLP method. The haplotypes 1T and 2C enhanced the risk for severe hepatotoxicity (OR=1.41,P=0.25;OR=1.67,P=0.31).IL-1β-511TT genotype significantly represented among tobacco using HIV-infected individuals compared to nonusers (OR=3.74,P=0.05).IL-1β-511TT genotype among alcohol users increased the risk for hepatotoxicity (OR=1.80,P=0.90).IL-1β-511CT and-511TT genotypes overrepresented in alcohol using HIV-infected individuals (OR=2.29,P=0.27;OR=2.64,P=0.19).IL-RN2/2 and 1/3 genotypes represented higher in nevirapine using hepatotoxicity patients (OR=1.42,P=0.64,OR=8.79,P=0.09).IL-1β-511CT and-511 TT genotypes among nevirapine users enhanced the risk for severe hepatotoxicity (OR=4.29,P=0.20;OR=1.95,P=0.56).IL-1β-511CT and-511TT genotypes were overrepresented in combined nevirapine and alcohol using HIV-infected individuals as compared to nevirapine users and alcohol nonusers (OR=2.56,P=0.26;OR=2.84,P=0.24).IL-1β-511TT genotype with tobacco, alcohol, and nevirapine usage revealed a trend of risk for the development of ARV-associated hepatotoxicity and its severity.

scholarly journals Tissue Inhibitor of Metalloproteinase-2 Polymorphisms and Risk for HIV-Associated Neurocognitive Disorder

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
HariOm Singh ◽  
Sushma Jadhav ◽  
Dharmesh Samani ◽  
Sumitra Nain
Keyword(s):  
Significant Risk ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Disease Stage ◽  
Neurocognitive Disorder ◽  
Healthy Controls ◽  
Hiv Disease ◽  
Hiv Patients ◽  
Pcr Rflp ◽  
And Gender ◽  
Alcohol Users

The imbalance between MMPs and TIMPs is associated with the HIV dissemination tissue damage pathology neurodegenerative disorders, including HAND. Genetic variations in the TIMP gene may modulate the neurocognitive disorder in HIV patients. Hence, we evaluated the genetic variants of TIMP-2 (-418G/C, 303G/A) gene with the risk of HAND. Genotyping of TIMP-2 polymorphism was performed in 50 patients with HAND, 100 no HAND, and 154 healthy controls by PCR-RFLP. TIMP-2 -418GC and 303AA genotypes represented a predominant risk for HAND severity (OR=1.55, P=0.30; OR=4.58, P=0.24). The variant -418CC genotype, -418A allele, had exhibited a significant risk for the acquisition of HAND (OR=12.55, P=0.026; OR=2.66, P=0.004). TIMP-2 303GA, 303AA genotype, and 303A allele evinced a higher risk for HAND severity (OR=1.82, P=0.14; OR=1.70, P=0.63; and OR=1.68, P=0.12). In HIV patients, TIMP-2 -418CC genotype and -418C allele significantly occurred in comparison to healthy controls (OR=10.10, P=0.006; OR=2.02, P=0.009). In the intermediate and early HIV disease stage, TIMP-2 -418CC genotype was significantly increased compared with healthy controls (11.1% vs. 1.3%, OR=14.63, P=0.01; 16.9% vs. 1.3%, OR=14.51, P=0.002). In patients with HAND among tobacco and alcohol users, TIMP-2 -418CC genotype displayed a risk for HAND severity (OR=3.96, P=0.26; OR=4.83, P=0.19). On multivariate logistic regression, TIMP-2 303AA genotype, advanced stage, and gender had a risk for HAND severity (OR=28.98, P=0.02; OR=2.35, P=0.070; and OR=2.36, P=0.04). In conclusion, TIMP-2 -418G/C polymorphism independently, along with alcohol and tobacco, may have an impact on the acquisition of HAND and its severity. TIMP-2 303G/A polymorphism bare a risk for HAND severity.

Alteration of tumor necrosis factor–α T-cell homeostasis following potent antiretroviral therapy: contribution to the development of human immunodeficiency virus–associated lipodystrophy syndrome

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3191-3198 ◽  
Author(s):  
Eric Ledru ◽  
Névéna Christeff ◽  
Olivier Patey ◽  
Pierre de Truchis ◽  
Jean-Claude Melchior ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 2 ◽  
Hiv Patients ◽  
Immunodeficiency Virus ◽  
Necrosis Factor

Abstract Highly-active antiretroviral therapy (HAART) has lead to a dramatic decrease in the morbidity of patients infected with the human immunodeficiency virus (HIV). However, metabolic side effects, including lipodystrophy-associated (LD-associated) dyslipidemia, have been reported in patients treated with antiretroviral therapy. This study was designed to determine whether successful HAART was responsible for a dysregulation in the homeostasis of tumor necrosis factor- (TNF-), a cytokine involved in lipid metabolism. Cytokine production was assessed at the single cell level by flow cytometry after a short-term stimulation of peripheral blood T cells from HIV-infected (HIV+) patients who were followed during 18 months of HAART. A dramatic polarization to TNF- synthesis of both CD4 and CD8 T cells was observed in all patients. Because it was previously shown that TNF- synthesis by T cells was highly controlled by apoptosis, concomitant synthesis of TNF- and priming for apoptosis were also analyzed. The accumulation of T cells primed for TNF- synthesis is related to their escape from activation-induced apoptosis, partly due to the cosynthesis of interleukin-2 (IL-2) and TNF-. Interestingly, we observed that LD is associated with a more dramatic TNF- dysregulation, and positive correlations were found between the absolute number of TNF- CD8 T-cell precursors and lipid parameters usually altered in LD including cholesterol, triglycerides, and the atherogenic ratio apolipoprotein B (apoB)/apoA1. Observations from the study indicate that HAART dysregulates homeostasis of TNF- synthesis and suggest that this proinflammatory response induced by efficient antiretroviral therapy is a risk factor of LD development in HIV+ patients.

scholarly journals TLR7 Polymorphism (rs179008 and rs179009) in HIV-Infected Individual Naïve to ART

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
HariOm Singh ◽  
Dharmesh Samani ◽  
Sumit Aggarwal
Keyword(s):  
Infected Individual ◽  
Univariate Analysis ◽  
Disease Stage ◽  
Rapid Decline ◽  
Healthy Controls ◽  
Single Nucleotide ◽  
Codominant Model ◽  
Pcr Rflp ◽  
Hiv 1 ◽  
Cd4t Cell

Toll-like receptors (TLRs) play an important role in the innate immune response to HIV infection. Single nucleotide polymorphism (SNP) in TLR7 (Gln11Leu) gene has been associated with a rapid decline of CD4T cell count. Hence, we assessed the TLR7 (rs179008, Gln11Leu (A/T) and rs179009, IVS2-151 (A/G)) polymorphism in 150 HIV-infected individuals naïve to ART and 158 healthy controls. The genotyping of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphisms was done using the PCR-RFLP method. In univariate analysis, none of the genotype and haplotype of TLR7 Gln11Leu (A/T) and IVS2-151 (A/G) polymorphism differed significantly between HIV-infected individuals and healthy controls. The occurrence of TLR7 rs179009AG genotype in the codominant model and rs179009 AG-GG genotype in the dominant model was significantly reduced in HIV-infected individuals as compared to healthy controls (18.0% vs. 29.1%, OR=0.42, P=0.016; 26.7% vs. 36.7%, OR=0.52, P=0.016). TLR7 rs179009AG genotype was significantly underrepresented in the intermediate HIV disease stage compared with healthy controls (OR=0.03, P=0.04). TLR7 rs179009AG genotype expressed higher in tobacco-consuming HIV-infected individuals compared with nonusers (OR=1.71, P=0.47). In conclusion, rs179009 AG-GG and AG genotypes were found reduced in HIV-infected individuals as compared to healthy controls; their higher prevalence in health individuals clearly support that they are associated with reduced risk of acquisition of HIV-1 infection.

Haplotype analysis of the matrix metalloproteinase 3 gene and myocardial infarction in a Chinese Han population

2004 ◽  
Vol 92 (10) ◽  
pp. 867-873 ◽  
Author(s):  
Xiaoyang Zhou ◽  
Jianfeng Huang ◽  
Jianhong Chen ◽  
Shaoyong Su ◽  
Runsheng Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Matrix Metalloproteinase ◽  
Promoter Polymorphism ◽  
Chinese Han Population ◽  
Healthy Controls ◽  
Chinese Han ◽  
Han Population ◽  
Matrix Metalloproteinase 3 ◽  
Increased Risk ◽  
The Matrix

SummaryMatrix metalloproteinase (MMP) 3 plays an important role in the pathogenesis of myocardial infarction (MI). Up to now, there has been conflicting data regarding the possible contribution of the MMP3 -1612 5A/6A promoter polymorphism to MI. In this study, we have investigated the possible association of three polymorphisms (-1612 5A/6A, -376C/G, Glu45Lys) in the MMP3 gene with MI in a Chinese Han population. The polymorphisms were analyzed in 509 patients with MI, and in 518 healthy controls. The frequency of the 5A allele was 14% in the healthy controls, which is less than in Western populations (40%-52%). Logistic regression analyses of individual polymorphisms indicated that individuals carrying the -1612 5A allele had an increased risk of MI (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.28 to 2.40), as did those carrying the -376 G allele (OR 1.78, 95% CI 1.33 to 2.38). The three polymorphisms studied were found to be in strong linkage disequilibria. Haplotype analyses showed that the 5A-G-Lys haplotype (-1612 5A, -376G and 45Lys) was independently associated with susceptibility to MI. Taken together, the effect of the MMP3 polymorphisms studied may be attributable to the -1612 5A/6A polymorphism. We conclude that the MMP3 -1612 5A/6A polymorphism is associated with MI in our population, implying that individuals of the 5A allele carriers have an increased risk of suffering MI.

scholarly journals Detection of soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1 in the effusion of otitis media with effusion

1995 ◽  
Vol 4 (5) ◽  
pp. 350-354 ◽  
Author(s):  
T. Ganbo ◽  
K.-I. Hisamatsu ◽  
H. Inoue ◽  
K. Kikushima ◽  
A. Mizukoshi ◽  
...  
Keyword(s):  
Otitis Media ◽  
Otitis Media With Effusion ◽  
Interleukin 2 ◽  
Intercellular Adhesion Molecule ◽  
Healthy Controls ◽  
Intercellular Adhesion Molecule 1 ◽  
Cytokine Network ◽  
Tnf Α ◽  
Soluble Interleukin 2 Receptor ◽  
Soluble Intercellular Adhesion Molecule

We measured sIL-2R, TNF-α and sICAM-1 in the sera and middle ear effusions (MEEs) of patients with otitis media with effusion (OME). Although there was no signmcant difference between the sIL-2R levels of the serous and mucoid MEEs, they were significantly higher than serum sIL-2R levels of OME patients and healthy controls. TNF-α levels of the mucoid MEEs were significantly higher than those of the serous type. However, TNF-α was rarely detected in the sera of OME patients or healthy controls. We observed significant differences between the serous and mucoid MEEs with respect to their sICAM-1 levels, which were also higher than serum slCAM-1 levels of OME patients and healthy controls. Our findings suggested that IL-2, TNF-α and ICAM-1 could be significantly involved in the pathogenesis of OME through the cytokine network.

scholarly journals Imaging the serotonin 1A receptor using [ 11 C]WAY100635 in healthy controls and major depression

2013 ◽  
Vol 368 (1615) ◽  
pp. 20120004 ◽  
Author(s):  
Natalie Hesselgrave ◽  
Ramin V. Parsey
Keyword(s):  
Response Prediction ◽  
Promoter Polymorphism ◽  
Binding Potential ◽  
Healthy Controls ◽  
Major Depressive ◽  
Genetic Components ◽  
Positron Emission ◽  
Temporal Model ◽  
Potential Tool ◽  
Treatment Response Prediction

As a neurotransmitter, serotonin (5-HT) is widely used throughout the brain and known to play a role in many processes including emotion and brain development. Of the 15 subtypes of 5-HT receptors, the 1A receptor (5-HT 1A ) has been implicated in depression and suicide. Using the [carbonyl- 11 C]WAY100635 ([ 11 C]WAY) ligand and positron emission tomography, we have studied the 5-HT 1A receptor, first in a group of healthy controls, then in two separate groups of subjects with major depressive disorder (MDD) (antidepressant exposed and not recently medicated), and, lastly, in a group of subjects remitted from MDD. All MDD subjects were medication-free at the time of scan. We found higher 5-HT 1A binding potential (BP F ) in MDD subjects not recently exposed to an antidepressant compared with controls and recently medicated MDD subjects; and higher BP F in subjects with the C(-1019)G promoter polymorphism. We replicated these findings in a novel cohort and reconciled our discrepant findings with other groups using alternate quantification techniques. We also reported higher BP F in subjects remitted from a major depressive episode than in controls. From this work, we proposed a temporal model in which 5-HT 1A BP F may be a trait abnormality of MDD. To further explore the genetic components of MDD and utility of 5-HT 1A imaging as a potential tool for biomarker or treatment response prediction, these findings should be replicated in a larger cohort using the [ 11 C]CUMI-101 agonist tracer.

Long-term effects of intermittent interleukin 2 therapy in patients with HIV infection: characterization of a novel subset of CD4+/CD25+ T cells

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2159-2167 ◽  
Author(s):  
Irini Sereti ◽  
Hector Martinez-Wilson ◽  
Julia A. Metcalf ◽  
Michael W. Baseler ◽  
Claire W. Hallahan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Cd4 T Cells ◽  
Interleukin 2 ◽  
Hiv Patients ◽  
Activation Markers ◽  
Cd25 Expression ◽  
Cell Counts

The long-term immunologic effects of intermittent interleukin 2 (IL-2) therapy were evaluated in a cross-sectional study by comparing 3 groups: HIV-seronegative volunteers, HIV-infected (HIV+) patients receiving highly active antiretroviral therapy (HAART), and HIV+ patients receiving HAART and intermittent IL-2. Whole-blood immunophenotyping was performed to study expression of the IL-2 receptor chains on T lymphocytes and natural killer cells and to further characterize CD4+/CD25+ T cells. Increased CD25 expression, especially in CD4+ T cells but also in CD8+ T cells, without increases in expression of the β and γ chains of the IL-2 receptor was detected in the IL-2 group. Up to 79% of naive CD4+ T cells (median, 61%) from patients in the IL-2 group expressed CD25, and the number of naive CD4+/CD25+ T cells correlated positively with both the total and naive CD4+ T-cell counts. A discrete population of CD45 double intermediate RA+/RO+CD4+ cells was also preferentially expanded in the IL-2 group, and the number of these cells strongly correlated with the total CD4+ count. Despite increases in CD25 expression, T lymphocytes from patients treated with IL-2 did not have increased expression of early (CD69) or late (CD95) activation markers or evidence of recent proliferation (Ki67). Both CD4+/CD25+ and CD4+/CD25− cells from IL-2–treated HIV+ patients proliferated in response to mitogens, specific antigens, and T-cell-receptor–mediated stimuli. Thus, intermittent administration of IL-2 in HIV+ patients leads to preferential expansion of a unique subset of CD4+ T cells that may represent a critical population in T-cell homeostasis.

Prognostic impact of the NFKB1 insertion/deletion promoter polymorphism on survival in patients with surgically resected gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15638-e15638
Author(s):  
S. Kim ◽  
J. Kim ◽  
Y. Chae ◽  
S. Sohn ◽  
J. Moon ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Disease Free Survival ◽  
Promoter Polymorphism ◽  
Prognostic Impact ◽  
Free Survival ◽  
Multivariate Survival ◽  
Pcr Rflp ◽  
Promoter Gene ◽  
Rflp Assay

e15638 Background: The present study analyzed the functional insertion/deletion polymorphism in the promoter region of NKFB1 gene and their impact on the prognosis for patients with gastric adenocarcinoma. Methods: Five hundred and three consecutive patients with surgically resected gastric adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and the -94 insertion/deletion ATTG polymorphism of NFKB1 determined using a PCR- RFLP assay. Results: The NFKB1 promoter gene polymorphism was successfully amplified in 97.8% of the cases. There were no sexual differences in relation to the genotype and allele. No correlation was observed between the frequency of the genotype or allele and the T, N, or M stage. The multivariate survival analysis showed no association between the NFKB1 -94 insertion/deletion promoter polymorphism and the disease-free survival or overall survival of the patients with gastric cancer. Conclusions: The functional NFKB1 promoter polymorphism was not found to be a prognostic marker for Korean patients with surgically resected gastric adenocarcinoma. No significant financial relationships to disclose.

scholarly journals A Family Screening of CD19 Gene Mutation by Restriction Fragment Length Polymorphism

2021 ◽  
Author(s):  
Mehmet Ali Karaselek ◽  
Hasan Kapaklı ◽  
Sukru Guner ◽  
Sevgi Keleş ◽  
Ismail Reisli
Keyword(s):  
B Lymphocyte ◽  
Index Case ◽  
Genetic Diagnosis ◽  
Newborn Baby ◽  
Fast Method ◽  
Healthy Controls ◽  
Heterozygous Genotype ◽  
First Case ◽  
Pcr Rflp ◽  
Homozygous Mutant

Background: CD19 molecule found on B lymphocyte surface forms CD19 complex together with CD21, CD81, CD225 in mature B cells and regulates B lymphocyte activation with antigen stimulation. Mutation(s) in the gene encoding the CD19 molecule affect CD19 protein expression and primary immunodeficiency (PID) occurs. Some genetic method, especially sanger and next generation sequencing and flow cytometric methods are widely used in the diagnosis of PID. The RFLP method, which is faster and cheaper than other mutation detection methods, is rarely used in the diagnosis of PID. The study aimed to genetically identify CD19 deficiency, which is a PID, using the RFLP method. Methods: The study was performed at Necmettin Erbakan University, Meram Medicine Faculty Hospital, Pediatric Allergy and Immunology clinic. A total of 8 patients and two healthy controls could be included in the study. A total of 8 patients and two healthy controls were included in the study, and the relevant region genotypes in the CD19 gene were determined by performing RCR-RFLP analysis. Results: CD19 deficiency was first described by us. The index case, newborn baby and mother were also included in the study. It was determined that the index case (P6) was homozygous mutant, the newborn baby (P7) and mother (P8) had heterozygous genotype. Based on this situation, one child (P1) was found to be homozygous mutant, mother (P2), father (P3) and other children (P4 and P5) had heterozygous genotype in the family, which was determined to be related to the first case. Conclusion: Rapid genetic diagnosis in patients suspected of having a known case of PID insufficiency as a result of clinical and laboratory findings carries a vital risk in terms of treatment options to be offered to patients. Although PCR-RFLP, which is a cheap, safe and fast method, is used to detect known mutations, the use of PID is rare. In our study, it has been shown that it is a method that can be used in the diagnosis of PID by determining genotypes using PCR-RFLP, and especially in terms of rapid genetic testing of family screenings.

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