Minor allele of Intercellular adhesion molecule-1 (ICAM-1) polymorphism (rs5498 1462A>G) is associated with SARS-CoV-2 infection and related mortality.
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ABSTRACT:
SUBMITTER: Padhi S
PROVIDER: S-EPMC8244367 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundRecently, associations between intercellular adhesion molecule-1 (ICAM-1) rs5498 polymorphism and ischemic stroke (IS) were investigated by several pilot studies, but with inconsistent results. In this study, a meta-analysis was performed to better assess the relationship between ICAM-1rs5498 polymorphism and IS.MethodsPubMed, Medline, Embase, and CNKI were searched for eligible studies. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate associations between ICAM-1 rs5498 polymorphism and IS.ResultsTotally 16 studies with 2,596 cases and 11,800 controls were analyzed. A significant association with IS was observed for rs5498 polymorphism in GG versus AA + AG (recessive model, p = 0.009, OR = 1.62, 95% CI 1.13-2.32, I2 = 76%) in overall population. Further subgroup analyses showed that rs5498 polymorphism was significantly associated with IS in Caucasians in AA versus AG + GG (dominant model, p = 0.03, OR = 0.52, 95% CI 0.29-0.95, I2 = 72%), GG versus AA + AG (recessive model, p < 0.0001, OR = 2.98, 95% CI 2.05-4.31, I2 = 19%), and A versus G (allele model, p = 0.005, OR = 0.50, 95% CI 0.31-0.81, I2 = 81%). However, no any positive findings were detected for Asians.ConclusionsOur findings indicated that rs5498 polymorphism was significantly associated with individual susceptibility to IS in Caucasians, but not in Asians.
| S-EPMC6565590 | biostudies-literature
Project description:In the present study, we included currently published evidence to comprehensively evaluate the influence of the rs5498 polymorphism within the ICAM1 (intercellular adhesion molecule 1) gene on the genetic risk of multiple sclerosis. STATA 12.0 software was utilized to carry out the heterogeneity assessment, association test, and Begg's test as well as the Egger's tests and sensitivity analyses. A total of 11 high-quality case-control studies were selected from the initially retrieved 2209 articles. The lack of high heterogeneity led to the use of a fixed-effect model in all genetic models. The results of the association test showed a reduced risk of multiple sclerosis in the allelic G vs A (P association = 0.036, OR = 0.91) and dominant AG+GG vs AA (P association = 0.042, OR = 0.85) but not in other genetic models (all P association > 0.05). In addition, the negative results were observed in further subgroup analyses based on ethnicity or Hardy-Weinberg equilibrium in all genetic models. Data from Begg's and Egger's tests further excluded the presence of remarkable publication bias, while sensitivity analysis data supported stable outcomes. Thus, we conclude that ICAM1 rs5498 may not be related to the risk of multiple sclerosis in Caucasian or Asian populations, which still merits further research.
| S-EPMC6294617 | biostudies-literature
Project description:BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) Lys469Glu (K469E) polymorphism and Gly 241Arg (G241R) polymorphism might play important roles in cancer development and progression. However, the results of previous studies are inconsistent. The aim of this study was to evaluate the association between ICAM-1 K469E and G241R polymorphisms and the risk of cancer by meta-analysis. METHODS: A comprehensive literature search (last search updated in November 2013) was conducted to identify case-control studies that investigated the association between ICAM-1 K469E and G241R polymorphisms and cancer risk. RESULTS: A total of 18 case-control studies for ICAM-1 polymorphisms were included in the meta-analysis, including 4,844 cancer cases and 5,618 healthy controls. For K469E polymorphism, no significant association was found between K469E polymorphism and cancer risk. However, subgroup analysis by ethnicity revealed one genetic comparison (GG vs. AA) presented the relationship with cancer risk in Asian subgroup, and two genetic models (GG+GA vs. AA and GA vs. AA) in European subgroup, respectively. For G241R polymorphism, G241R polymorphism was significantly association with cancer risk in overall analysis. The subgroup analysis by ethnicity showed that G241R polymorphism was significantly associated with cancer risk in European subgroup. CONCLUSION: ICAM-1 G241R polymorphism might be associated with cancer risk, especially in European populations, but the results doesn't support ICAM-1 K469E polymorphism as a risk factor for cancer.
| S-EPMC4537618 | biostudies-literature
Project description:BackgroundMany studies investigated the association between intercellular adhesion molecule 1 (ICAM-1) gene rs5498 polymorphism and the risk of coronary artery disease (CAD). However, the results were inconsistent.MethodsTo clarify convincing association, we conducted a comprehensive meta-analysis by searching in PubMed, Embase, Web of sciences, Sciences citation index, Google scholar, Cochrane Library, and the CNKI databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsA total of 29 case-control studies with 5,494 cases and 6,364 controls for rs5498 polymorphism were included. The studied populations of this meta-analysis included Caucasians and Asians. Meta-analysis showed that rs5498 polymorphism was associated with the decreased risk of CAD. Stratification analysis of ethnicity found that rs5498 polymorphism decreased the risk of CAD among Caucasians, but not among Asians. Stratification by type of CAD revealed that ICAM-1 gene rs5498 polymorphism was also correlated with the decreased risk of myocardial infarction (MI).ConclusionIn conclusion, this meta-analysis indicates that ICAM-1 gene rs5498 polymorphism decreases the risk of CAD.
| S-EPMC6200538 | biostudies-literature
Project description:The interaction between integrin lymphocyte function-associated antigen-1 (LFA-1) and its ligand intercellular adhesion molecule-1 (ICAM-1) is critical in immunological and inflammatory reactions but, like other adhesive interactions, is of low affinity. Here, multiple rational design methods were used to engineer ICAM-1 mutants with enhanced affinity for LFA-1. Five amino acid substitutions 1) enhance the hydrophobicity and packing of residues surrounding Glu-34 of ICAM-1, which coordinates to a Mg2+ in the LFA-1 I domain, and 2) alter associations at the edges of the binding interface. The affinity of the most improved ICAM-1 mutant for intermediate- and high-affinity LFA-1 I domains was increased by 19-fold and 22-fold, respectively, relative to wild type. Moreover, potency was similarly enhanced for inhibition of LFA-1-dependent ligand binding and cell adhesion. Thus, rational design can be used to engineer novel adhesion molecules with high monomeric affinity; furthermore, the ICAM-1 mutant holds promise for targeting LFA-1-ICAM-1 interaction for biological studies and therapeutic purposes.
| S-EPMC1455478 | biostudies-literature
Project description:Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The anti-diabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of anti-apoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.
| S-EPMC8789909 | biostudies-literature
Project description:The immunoglobulin (Ig) superfamily is one of the largest families in the vertebrate genome, found most frequently in cell surface molecules. Intercellular adhesion molecule-1 (ICAM-1) contains five extracellular Ig superfamily domains (D1-D5) of which the first domain, D1, is the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-1) and human rhinovirus. Despite the modular nature of many Ig superfamily domains with respect to domain folding and ligand recognition, D1 does not fold on its own due to the loss of its interaction with the second domain. The goal of this study was to engineer ICAM-1 D1 by introducing mutations that would stabilize the Ig superfamily domain fold while retaining its ability to bind to LFA-1 and rhinovirus. First, with a directed evolution approach, we isolated mutations in D1 that showed binding to conformation-specific antibodies and the ligand binding domain of LFA-1 called the inserted, or I, domain. Then, with a rational design approach we introduced mutations that contributed to the stability of ICAM-1 D1 in solution. The mutations that restored native folding of D1 in isolation were those that would convert hydrogen bond networks in buried regions into hydrophobic contacts. Notably, for most mutations, identical or similar types of substitutions were found in ICAM-1 molecules of different species and other ICAM family members. The systematic approach demonstrated in this study to engineer a single Ig superfamily fold in ICAM-1 can be broadly applicable to the engineering of modular Ig superfamily domains in other cell surface molecules.
| S-EPMC2871458 | biostudies-literature
Project description:Paeoniflorin (PF) has ameliorative effects on learning and memory impairment and cerebral ischaemia in rats and has protective effects against the degeneration of dopaminergic neurons in substantia nigra. The neuroprotective effects of PF are most probably derived from its anti-inflammatory property. Abnormally high levels of intercellular adhesion molecule-1 (ICAM-1) have been found to be associated with a wide range of inflammatory and immune responses. Here we studied whether PF regulates the levels of ICAM-1 elevated in LPS-activated differentiated human monocytic U937 cells and TNF-?-stimulated human umbilical vein endothelial cells (HUVECs).mRNA levels were evaluated by RT-PCR. Protein levels were evaluated by Western blot analysis. An immunofluorescence technique was used to estimate NF-?B translocation, and NF-?B binding to nuclear DNA was determined by EMSA.PF inhibited ICAM-1 expression elevated in LPS-induced U937 cells and TNF-?-stimulated HUVECs. Although previous reports showed that PF's action is mediated by activating adenosine A? receptors, application of a selective adenosine A? receptor antagonist did not change the inhibitory effect of PF in our experiments. To elucidate the underlying mechanisms of the effect of PF, we studied its effect on signalling pathways upstream of ICAM-1 expression. PF suppressed the activation of the NF-?B pathway, which regulates the expression of ICAM-1. The TLR4 and MAPK pathways were shown not to be involved in the effects of PF in these cells.PF inhibits ICAM-1 expression in LPS-treated U937 cells and TNF-?-stimulated HUVECs by suppressing the activation of the NF-?B pathway.
| S-EPMC3188904 | biostudies-other
Project description:Many human inherited disorders cause protein N-glycosylation defects, but there are few cellular markers to test gene complementation for such defects. Plasma membrane glycoproteins are potential biomarkers because they may be reduced or even absent in plasma membranes of glycosylation-deficient cells. We combined stable isotope labeling by amino acids in cell culture (SILAC) with linear ion trap mass spectrometry (LTQ Orbitrap(TM)) to identify and quantify membrane proteins from wild-type CHO and glycosylation-deficient CHO (Lec9) cells. We identified 165 underrepresented proteins from 1447 unique quantified proteins, including 18 N-glycosylated plasma membrane proteins. Using various methods, we found that intercellular cell adhesion molecule 1 (ICAM-1) was reduced in Lec9 cells and in fibroblasts from 31 congenital disorder of glycosylation (CDG) patients compared with normal controls. Mannose supplementation of phosphomannose isomerase-deficient CDG-Ib (MPI-CDG) cells and complementation with PMM2 in PMM2-deficient CDG-Ia (PMM2-CDG) cells partially corrected hypoglycosylation based on increased ICAM-1 presence on the plasma membrane. These data indicate that ICAM-1 could be a useful hypoglycosylation biomarker to assess gene complementation of CDG-I patient cells and to monitor improved glycosylation in response to therapeutic drugs.
| S-EPMC3365753 | biostudies-literature
Project description:Oral squamous cell carcinoma has a striking tendency to migrate and metastasize. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. However, the effects of COX-2 on human oral cancer cells are largely unknown. We found that overexpression of COX-2 or exogenous PGE(2) increased migration and intercellular adhesion molecule 1 (ICAM)-1 expression in human oral cancer cells. Using pharmacological inhibitors, activators, and genetic inhibition of EP receptors, we discovered that the EP1 receptor, but not other PGE receptors, is involved in PGE(2)-mediated cell migration and ICAM-1 expression. PGE(2)-mediated migration and ICAM-1 up-regulation were attenuated by inhibitors of protein kinase C (PKC)?, and c-Src. Activation of the PKC?, c-Src, and AP-1 signaling pathway occurred after PGE(2) treatment. PGE(2)-induced expression of ICAM-1 and migration activity were inhibited by a specific inhibitor, siRNA, and mutants of PKC?, c-Src, and AP-1. In addition, migration-prone sublines demonstrated that cells with increased migration ability had higher expression of COX-2 and ICAM-1. Taken together, these results indicate that the PGE(2) and EP1 interaction enhanced migration of oral cancer cells through an increase in ICAM-1 production.
| S-EPMC2943269 | biostudies-literature