Intercellular Adhesion Molecule-1 Rs5498 Research Articles

Genetic Association of ICAM-1 (rs5498) Gene Polymorphism With Susceptibility to Stage II Grade B Periodontitis: A Case-Control Study in South Indian Population.

In the contemporary perspective, periodontitis is considered a complex issue triggered and perpetuated by bacteriabut strongly influenced by the way the body reacts to bacterial plaque. Recent research has indicated that variations in genes might have an impact on the development of periodontitis. This study was conducted to explore a probable link between the genetic variations in intercellular adhesion molecule-1 (ICAM-1) represented by rs5498 and the occurrence of periodontitis. Methods: A total of 100 participants, 50 with periodontitis and 50 with periodontally healthy or mild gingivitis, were recruited for this study. Whole blood drawn from the participants was used to obtain genomic DNA. The ICAM-1 gene polymorphism (rs5498) was determined using polymerase chain reaction (PCR) amplification and digestion. The ICAM-1 gene's flanking primers were used to amp up the DNA. For statistical analysis, the genotype that was analyzed using the pattern of restriction fragment length polymorphism was recorded. The Chi-square test compared genotype and allele frequency distributions between both groups. The odds ratio with 95% confidence intervals with each individual allele or genotype was used to compute the risk. Statistical significance was established in all tests when the p-value was less than 0.05. There was no discernible difference between the genotype frequencies of patients and controls χ2df (P = 0.6065). The findings demonstrated that no significant difference was present between the two groups for homozygous or heterozygous mutant genotypes (AA vs. AG+GG; P = 0.6854). There was no discernible difference in the detected frequencies of the A allele (58% vs. 61%), G allele (42% vs. 39%), TT (16% vs. 24%), AG (40% vs. 36%), and TT genotypes in the studied groups. According to the results of the current investigation, the ICAM-1 (rs5498) gene polymorphism is not associated with periodontitis in the population investigated.

Association of ITGA4 and ICAM-1 gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease

To assess the association between the polymorphism of integral protein α4 (ITGA4) and intercellular adhesion molecule 1 (ICAM-1) genes and the risk and clinicopathological characteristics of Crohn's disease (CD) among Chinese patients. From January 2010 to January 2021, a total of 215 CD patients and 529 gender- and age-matched healthy controls were enrolled from the Second Affiliated Hospital of Wenzhou Medical University as the study subjects. Genotypes of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) were determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Harvey-Bradshaw Index (HBI) was applied to assess the disease activity of CD, and the patients were further divided into subgroups based on the Montreal Classification Criteria of CD. Unconditional logistic regression was employed to analyze the distribution of ITGA4 (rs6740847, rs7562325) and ICAM-1 (rs5498) polymorphisms between the patients and healthy controls and their association with the clinicopathological characteristics of the patients. The frequencies of T allele and CT+TT genotypes of ITGA4 (rs7562325) were higher in CD patients than the healthy controls (40.70% vs. 31.57%, P = 0.001; 62.79% vs. 54.36%, P = 0.042). The G variant and AG+GG genotypes of ITGA4 (rs6740847) were less common in patients with moderately to severely active CD compared with those with mildly active CD (31.18% vs. 51.72%, P = 0.002; 55.91% vs. 75.86%, P = 0.042). However, the opposite conclusion was drawn for the G allele (G) and AG+GG genotypes of ICAM-1 (rs5498) (31.45% vs. 17.24%, P = 0.027; 54.30% vs. 31.04%, P = 0.020). Compared with patients with terminal ileal or ileocolic CD, G allele and AG+GG genotypes of ITGA4 (rs6740847) were more prevalent in patients with colonic CD (55.26% vs. 29.38%, P < 0.001; 84.21% vs. 53.11%, P<0.001). The same conclusion could also be drawn for the G allele and AG+GG genotypes of ICAM-1 (rs5498) (42.11% vs. 26.84%, P = 0.008; 73.69% vs. 46.33%, P = 0.002). The frequency of homozygous GG genotype of ICAM-1 (rs5498) was lower in patients with stricturing and penetrating CD than those with non-stricturing and non-penetrating CD (0.00% vs. 12.32%, P = 0.001). The G allele and AG+GG genotypes of the ITGA4 (rs6740847) were more common in patients with perianal lesions than those without (40.28% vs. 30.77%, P = 0.049; 72.22% vs. 51.75%, P = 0.004). Variants of the ITGA4 (rs7562325) may be a risk factor for CD, whilst those of the ITGA4 (rs6740847) may be associated with the decline of disease activity and risk for colon involvement and perianal lesions. Variants of the ICAM-1 (rs5498) may increase the risk of disease activity and colonic involvement in CD patients, however, it may be a protective factor for stenosis and penetration. In addition, variants of the ITGA4 (rs6740847) and ICAM-1 (rs5498) may be associated with the early onset of CD.

Pharmacogenetics in Model-Based Optimization of Bevacizumab Therapy for Metastatic Colorectal Cancer.

Vascular endothelial growth factor A (VEGF-A) and intercellular adhesion molecule 1 (ICAM-1) are significant regulators of angiogenesis, an important biological process involved in carcinogenesis. Bevacizumab, an anti-VEGF monoclonal antibody (MAB), is approved for the treatment of metastatic Colorectal cancer (mCRC), however clinical outcomes are highly variable. In the present study, we developed a pharmacokinetic (PK), a simplified quasi-steady state (QSS) and a pharmacokinetic/pharmacodynamic (PK/PD) model to identify potential sources of variability. A total of 46 mCRC patients, who received bevacizumab in combination with chemotherapy were studied. VEGF-A (rs2010963, rs1570360, rs699947) and ICAM-1 (rs5498, rs1799969) genes’ polymorphisms, age, gender, weight, and dosing scheme were investigated as possible co-variates of the model’s parameters. Polymorphisms, trough, and peak levels of bevacizumab, and free VEGF-A were determined in whole blood and serum. Data were analyzed using nonlinear mixed-effects modeling. The two-compartment PK model showed that clearance (CL) was significantly lower in patients with mutant ICAM-1 rs1799969 (p < 0.0001), inter-compartmental clearance (Q) was significantly higher with mutant VEGF-A rs1570360 (p < 0.0001), and lower in patients with mutant VEGF-A rs699947 (p < 0.0001). The binding QSS model also showed that mutant ICAM-1 rs1799969 was associated with a lower CL (p = 0.0177). Mutant VEGF-A rs699947 was associated with a lower free VEGF-A levels, prior to the next dose (p = 0.000445). The above results were confirmed by the PK/PD model. Findings of the present study indicated that variants of the genes regulating angiogenesis might affect PK and PD characteristics of bevacizumab, possibly influencing the clinical outcomes.

A Allele of ICAM-1 Rs5498 and VCAM-1 Rs3181092 is Correlated with Increased Risk for Periodontal Disease.

ObjectivePeriodontal disease (PD) is viewed today as multifactorial problems initiated and sustained by bacteria but significantly modified by the body’s response to bacterial plaque. Recent studies have suggested that gene polymorphisms could be involved in the pathophysiology of periodontitis. This study aimed to investigate a possible correlation of the polymorphisms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) with PD.MethodsThe genotypes of ICAM-1 and VCAM-1 were initially determined in PD patients using denaturing high performance liquid chromatography (DHPLC). ELISA was then conducted to measure ICAM-1 and VCAM-1 protein levels. Next, the association of ICAM-1/VCAM-1 genotype distribution and expression with clinical indicators and severity of PD was analyzed.ResultsPD patients contained increased levels of hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL), increased ICAM-1 and VCAM-1 protein levels, and decreased high-density lipoprotein (HDL) level. The GG genotype and G allele at ICAM-1 rs5498, as well as the AG and GG genotypes and G allele at VCAM-1 rs3181092 may reduce PD risk.ConclusionTo sum up, the overexpressed ICAM-1 and VCA M-1 as well as A allele of ICAM-1 rs5498 and VCAM-1 rs3181092 is associated with the onset of PD.

The K469E genetic variant in the ICAM1 gene is associated with type 2 diabetes but not with its vascular complications: a meta-analysis

Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by diminished insulin secretion and hyperglycemia leading to damage of multiple organs. The present study is aimed to test the association between type 2 diabetes vascular complications and K469E variant (rs5498) of the intercellular adhesion molecule-1 (ICAM1) gene. Methods: Online databases were searched to retrieve all publications relating to the ICAM1 rs5498 variant in human diabetic vascular complications. In the present meta-analysis, we included all eligible studies and calculated the pooled results using MetaGenyo web tool. Results: Studies concerning ICAM1 gene K469E variant association with either type 2 diabetes or diabetes related vascular complications were included in this meta-analysis. Fifteen articles were included in this analysis (n=10 for T2DM; n=5 for diabetes nephropathy; n=8 for diabetes retinopathy). ICAM1 K469E variant significantly increased the risk of T2DM in the allelic (OR = 1.10, 95% CI: 1.01-1.20, P = 0.032) and recessive models (OR = 1.27, 95% CI: 1.08-1.49, P = 0.004). However, the ICAM1 gene K469E variant is not associated with diabetic nephropathy or diabetic retinopathy. No noticeable evidence of publication bias was detected. Conclusion: In summary, our study indicated that ICAM1 K469E variant was significantly associated with the increased risk of diabetes but not with the diabetic vascular complications.

The influence of ICAM1 rs5498 on diabetes mellitus risk: evidence from a meta-analysis.

Both type 1 diabetes (T1D) and type 2 diabetes (T2D) are classified as forms of diabetes mellitus (DM) and commonly considered inflammatory process. Intercellular adhesion molecule-1 (ICAM-1) is involved in the development and progression of diabetes mellitus. However, the genetic association between ICAM-1 rs5498, and T1D and T2D risk was inconclusive. A meta-analysis by searching the PubMed, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) databases was performed out. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to describe the strength of association of T1D and T2D risk. A total of 14 studies encompassing 3233 cases and 2884 controls were included in the present meta-analysis. Significant associations were found between the allele and recessive models of ICAM1 rs5498 and DM in Asian population (allele: OR 1.13; 95% CI 1.03-1.23, p = 0.008; recessive: OR 1.25; 95% CI 1.06-1.48, p = 0.008), but not in Caucasian population (p > 0.05). In addition, the allele model of rs5498 was found to be significantly associated with the increased risk of T2D (OR 1.10; 95% CI 1.01-1.21, p = 0.03), but not T1D (p > 0.05). The ICAM1 rs5498 might be a susceptible factor for T2D, but not T1D. And the allele and recessive models of ICAM1 rs5498 might be a risk factor in Asian population.

The genetic effect of the ICAM1 (intercellular adhesion molecule 1) rs5498 polymorphism on the susceptibility towards multiple sclerosis.

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 (Passociation = 0.036, OR = 0.91) and dominant AG+GG vs AA (Passociation = 0.042, OR = 0.85) but not in other genetic models (all Passociation > 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.

Association between E469K polymorphism in the ICAM1 gene and the risk of diabetic nephropathy: a meta-analysis

BackgroundInflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN). Intercellular adhesion molecule 1 (ICAM1) is an acute phase marker of inflammation. ICAM1 rs5498 has been reported to be associated with the risk of DN. However, the previous findings were conflicting due to the limited sample sizes, different methodologies and ethnicities. Therefore, this study aimed to investigate the genetic association between ICAM1 rs5498 and the risk of DN.MethodsTwo investigators independently searched the studies from the databases PubMed, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Embase. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the associations.ResultsNo significant association was detected between ICAM1 rs5498 and DN susceptibility in allelic and recessive models (p > 0.05). However, significant reduction of frequencies of the dominant model of ICAM1 rs5498 was only detected in the Caucasian subgroup (OR = 0.80; 95% CI = [0.65, 0.99], p = 0.04) and type 1 diabetes mellitus subgroup (OR = 0.80; 95% CI = [0.65, 0.99], p = 0.04).ConclusionsThus, ICAM1 rs5498 might be a risk factor for DN in Caucasians and type 1 diabetes mellitus patients, which suggested that ICAM1 rs5498 might help in early diagnosis and prevention of this disease. Further studies were needed to clarify the biochemical function and pathological role of ICAM1 rs5498 in the risk of DN.

Association between diabetic retinopathy in type 2 diabetes and the ICAM-1 rs5498 polymorphism: a meta-analysis of case-control studies

BackgroundGenetic studies have reported contradictory results on the association between the intercellular adhesion molecule-1 (ICAM-1) rs5498 polymorphism and diabetic retinopathy (DR) risk in type 2 diabetic patients. We aimed to perform a systematic literature search and conduct random-effects meta-analysis to provide a quantitative evaluation.MethodsWe searched Pubmed, Embase, Scopus, Web of Science and Wanfang databases from inception up to January 2018. Allelic and genotype frequencies of rs5498 was compared between DR cases and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model.ResultsNine studies involving a total of 1792 cases and 1400 controls met our inclusion criteria. We did not find any significant association between rs5498 and DR risk at the dominant model (GG + GA versus AA, OR = 1.00, 95% CI: 0.66–1.50, P = 0.987), the recessive model (GG versus GA + AA, OR = 1.24, 95% CI: 0.86–1.77, P = 0.245), the GG versus AA contrast (OR = 1.14, 95% CI: 0.68–1.92, P = 0.611), and the G allele versus A allele contrast (OR = 1.08, 95% CI: 0.81–1.45, P = 0.592). Subgroup analysis by ethnicity showed no association in Asian populations (G allele versus A allele: OR = 1.05, 95% CI: 0.76–1.44, P = 0.790). Subgroup analysis by DR subtype also did not reveal any association of rs5498 with proliferative DR (G allele versus A allele: OR = 1.34, 95% CI: 0.71–2.52, P = 0.364) and non-proliferative DR (G allele versus A allele: OR = 0.71, 95% CI: 0.43–1.17, P = 0.180).ConclusionOur meta-analyses provide no evidence of the association of rs5498 with DR in type 2 diabetic patients.

Functional variants in intercellular adhesion molecule-1 and toll-like receptor-4 genes are more frequent in children with febrile urinary tract infection with renal parenchymal involvement.

We studied the functional polymorphisms of intercellular adhesion molecule-1 (ICAM-1) and toll-like receptor-4 (TLR-4) genes and risk of acute pyelonephritis (APN) in children attending Assiut University Children's Hospitals, Egypt, from 2011 to 2015. Urinary tract infections (UTIs) were diagnosed in 380 children: 98 had APN and 282 had lower UTIs. Four single-nucleotide polymorphisms in ICAM-1 and TLR-4 genes were genotyped in all subjects: ICAM-1 rs1799969 Gly241Arg, ICAM-1 rs5498 Glu469Lys, TLR-4 rs4896791 Thr399Ile and TLR-4 rs4896790 Asp299Gly. Patients with APN were significantly more likely to have AA genotype of the ICAM-1 rs5498 (1462 A/G) polymorphism (p=0.04) than children with lower UTIs and the TLR-4 Asp299Gly GG genotype (p=0.002) and G allele (p=0.006) than healthy controls. The association with the ICAM-1 Glu469Lys (1462A/G) was less evident. The GG genotype was associated with a modest relative risk of 1.4 (p=0.1) of developing APN, but was not an independent odds ratio, at 1.2 (p=0.48). Functional variants in ICAM-1 and TLR-4 genes were increasingly common in children with febrile UTIs with renal parenchymal involvement, but the ICAM-1 Glu469Lys (1462A/G) association was less evident. TLR4 Asp299Gly might independently increase renal parenchymal infection rather than renal scarring.

Intercellular adhesion molecule 1 rs5498 polymorphism is associated with the risk of myocardial infarction.

Several studies addressed the association between Intercellular adhesion molecule 1 (ICAM-1) rs5498 polymorphism and Myocardial Infarction (MI) risk. However, they addressed conflicting findings. Therefore, the aim of this study was to explore whether ICAM-1 gene rs5498 polymorphism plays an important role in modifying the risk of MI. A meta-analysis was conducted on the association between ICAM-1 rs5498 polymorphism and MI. 12 eligible studies involving 1,696 cases and 3,039 controls were included in the meta-analysis. Meta-analysis revealed that ICAM-1 rs5498 polymorphism showed a strongly positive correlation with MI and could be viewed as a protective factor for MI. Furthermore, subgroup analysis according to ethnicity indicated that ICAM-1 rs5498 polymorphism decreased the risk of MI among Caucasian and Asian populations. In conclusion, ICAM-1 rs5498 polymorphism was associated with the decreased risk of MI. Larger sample size studies with more diverse ethnic populations are needed to confirm these findings.

Single-Nucleotide Polymorphisms and Haplotypes of Intercellular Adhesion Molecule-1 in Uterine Cervical Carcinogenesis in Taiwanese Women.

The association of intercellular adhesion molecule 1 (ICAM-1) genetic polymorphisms with uterine cervical carcinogenesis has seldom been reported. Therefore, the aim of this study was to investigate the association of single-nucleotide polymorphisms (SNPs) and haplotypes of ICAM-1 with cervical tumorigenesis in Taiwanese women. Four hundred forty four women, including 91 with cervical invasive cancer, 63 with precancerous lesions, and 290 normal controls, were recruited. The genotypic distribution of 4 SNPs of ICAM-1, rs5498 (A1548G), rs5491 (K56M), rs281432 (C8823G), and rs3093030 (C-286T) was determined using real-time polymerase chain reactions and genotyping. Compared to homozygous wild CC, heterozygous CG, homozygous mutant GG, or genotypes with CG/GG display increased risks or a tendency of precancerous lesions or invasive cancer with strong power in rs281432. The homozygotic mutant alleles TT in rs3093030 and homozygotic mutant alleles GG in rs5498 were associated with a higher risk of invasive cancer and precancerous lesions, respectively, but with lower power. The CG/TA/TG haplotypes of ICAM-1 SNPs rs3093030 and rs5498 exhibited a tendency to increase susceptibility to precancerous lesions and invasive cancer. In conclusion, Taiwanese women with ICAM-1 SNP rs281432 and haplotypes CG/TA/TG of rs3093030 and rs5498 are associated with uterine cervical carcinogenesis.

Association of intercellular adhesion molecule-1 single nucleotide polymorphisms with hepatocellular carcinoma susceptibility and clinicopathologic development.

Intercellular adhesion molecule-1 (ICAM-1) is a human protein encoded by the ICAM-1 gene and is typically expressed on endothelial cells and immune cells. ICAM-1 is associated with episode, growth, invasion, and metastasis of hepatocellular carcinoma (HCC). However, the association between ICAM-1 genetic variants and the risk of HCC is undetermined. In this study, we investigated the potential associations of ICAM-1 single nucleotide polymorphisms (SNPs) with susceptibility to HCC and its clinicopathological characteristics. A total of 918 participants, including 613 controls participants and 305 patients with HCC, were selected for the analysis of ICAM-1 SNPs (rs3093030, rs5491, rs281432, and rs5498) by using real-time PCR genotyping. After adjusting for covariants of age, sex, and alcohol consumption, 125 smoker patients with HCC carrying at least one G genotype (AG and GG) in rs5498 were observed to have a higher HCC risk compared with 231 smoker control participants carrying the wild-type allele AA (adjusted odds ratio (AOR), 1.713; 95% confidence interval (CI), 1.091-2.690; P = 0.019). However, patients who possess at least one polymorphic allele of rs5498 are less prone to develop vascular invasive (AOR, 0.309; 95% CI, 0.103-0.926; P = 0.036). The results suggest that the genetic polymorphism in ICAM-1 rs5498 SNPs with genotype AG and GG is associated with HCC risk among smokers. Moreover, gene and environment interactions of ICAM-1 rs5498 polymorphisms might alter susceptibility to liver cancer. Therefore, ICAM-1 rs5498 may serve as a marker to predict the vascular invasion risk in smoker patients with HCC.

Integrative genomic analysis identifies a role for intercellular adhesion molecule 1 in childhood asthma

Childhood asthma is characterized by chronic airway inflammation. Integrative genomic analysis of airway inflammation on genetic and protein level may help to unravel mechanisms of childhood asthma. We aimed to employ an integrative genomic approach investigating inflammation markers on DNA, mRNA, and protein level at preschool age in relationship to asthma development. In a prospective study, 252 preschool children (202 recurrent wheezers, 50 controls) from the Asthma DEtection and Monitoring (ADEM) study were followed until the age of six. Genetic variants, mRNA expression in peripheral blood mononuclear cells, and protein levels in exhaled breath condensate for intercellular adhesion molecule 1 (ICAM1), interleukin (IL)4, IL8, IL10, IL13, and tumor necrosis factor α were analyzed at preschool age. At six years of age, a classification (healthy, transient wheeze, or asthma) was based on symptoms, lung function, and medication use. The ICAM1 rs5498 A allele was positively associated with asthma development (p=0.02) and ICAM1 gene expression (p=0.01). ICAM1 gene expression was positively associated with exhaled levels of soluble ICAM1 (p=0.04) which in turn was positively associated with asthma development (p=0.01). Furthermore, rs1800872 and rs1800896 in IL10 were associated with altered IL10 mRNA expression (p < 0.01). Exhaled levels of IL4, IL10, and IL13 were positively associated with asthma development (p < 0.01). In this unique prospective study, we demonstrated that ICAM1 is associated with asthma development on DNA, mRNA, and protein level. Thus, ICAM1 is likely to be involved in the development of childhood asthma.

Association of cell adhesion molecule gene polymorphisms with recurrent aphthous stomatitis

Recurrent aphthous stomatitis (RAS) is a common oral ulcerative condition. At ulcer sites vascular adhesion molecule-1 (VCAM-1), E-selectin and intercellular adhesion molecule-1 (ICAM-1) are strongly expressed on blood vessels, and ICAM-1 is expressed on keratinocytes. Expression of these molecules would promote leukocyte accumulation and invasion of the epithelium. Thus, polymorphisms in these candidate genes might contribute to RAS susceptibility. We investigated whether the inheritance of specific selectin, ICAM and VCAM gene polymorphisms is associated with RAS susceptibility. Ninety-six RAS cases and 153 controls were recruited from a Jordanian population. Blood was collected for hematological investigations and genotyping. Six SNPs were genotyped: E-selectin rs5361 and rs1805193, L-selectin, rs2205849, ICAM-1 rs5498, ICAM-5 rs885743 and VCAM-1 rs1800821. Association was determined using chi-square and binary logistic regression analysis after correcting for confounding factors. Linkage disequilibrium was determined using the EH program, and the Phase 2.1 program was used to construct and compare haplotypes between cases and controls. There was a significant association of the A allele (Pcorr =0.027), AA and AC genotypes (OR=10.9 and 9.0, respectively) of the E-selectin rs5361 gene polymorphism and TAA haplotype (rs2205849, rs5361, and rs1805193, respectively; P=0.03) with RAS. None of the other SNPs showed a significant association. This is the first report to link inheritance of the A allele, AA and AC genotypes of the E-selectin rs5361 polymorphism with increased risk of RAS. Further studies in different patient cohorts are needed to confirm the association, and functional analyses might clarify the biological significance of the association.