Intercellular Adhesion Molecule-1 Gene Polymorphisms Research Articles

Analysis of ICAM-1 rs3093030, VCAM-1 rs3783605, and E-Selectin rs1805193 Polymorphisms in African Women Living with HIV and Preeclampsia.

Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin are cell adhesion molecules that play a significant role in inflammation and are implicated in the pathophysiology of preeclampsia development and HIV infection. More specifically, the immune expression of ICAM-1, VCAM-1, and E-selectin within cyto- and syncytiotrophoblast cells are dysregulated in preeclampsia, indicating their role in defective placentation. This study investigates the associations of ICAM-1, VCAM-1, and E-selectin gene variants (rs3093030, rs3783605, and rs1805193, respectively) with preeclampsia comorbid with HIV infection in women of African ancestry. It also examines the susceptibility to preeclampsia development and the effect of highly active antiretroviral therapy (HAART). A total of 405 women were enrolled in this study. Out of these women, 204 were preeclamptic and 201 were normotensive. Clinical characteristics were maternal age, weight, blood pressure (systolic and diastolic), and gestational age. Whole blood was collected, DNA was extracted, and genotyping of the ICAM-1 (rs3093030 C>T), VCAM-1(rs3783605 A>G), and E-selectin (rs1805193 A>C) gene polymorphisms was performed. Comparisons were made using the Chi-squared test. Our results demonstrated that preeclamptic women exhibited a higher frequency of analyzed variants, in contrast to those with the duality of preeclampsia and HIV infection. Additionally, the C allele of the ICAM-1 (rs3093030 C>T) and G allele of the VCAM-1 (rs3783605 A>G) genes were found to have a greater role in the co-morbidity and may be considered as a risk factor for preeclampsia development in women of African ancestry. In contrast, the SNP of rs1805193 of the E-selectin gene indicated that A>C was only significantly associated with HIV infection and not with preeclampsia. These findings highlight a strong association of the rs3093030 SNP of the ICAM-1 gene and of the VCAM-1 rs3783605 gene with the development of preeclampsia, indicating their role in the defective trophoblast invasion of preeclampsia. Sub-group analysis further reveals an association of the AA genotype with late-onset preeclampsia, a less severe form of disease indicating differing genetic predispositions between early and late-onset forms.

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.

Intercellular Adhesion Molecule-1 Gene Polymorphisms and Susceptibility to Cervical Cancer in the Northern Chinese Han Population.

Many epidemiological studies have confirmed that ICAM-1 gene single-nucleotide polymorphisms (SNPs) are associated with susceptibility of various cancers, but there are relatively few studies on the relationship between ICAM-1 gene polymorphisms and the risk of cervical cancer. Therefore, we aimed to explore the potential role of ICAM-1 gene polymorphisms and the combined effect of SNPs in the pathogenesis of cervical cancer in Han women in northern China. This case–control group includes 488 cases of cervical cancer, 684 cases of cervical precancerous lesions, and 510 healthy females. Multiplex polymerase chain reaction (PCR) combined with the next-generation sequencing method was used for the determination of gene polymorphisms (rs5498, rs3093030, and rs281432). In our study, we divide cervical cancer into two subgroups: cervical squamous cell carcinoma (CSCC) group and cervical adenocarcinoma (CAC) group. We analyzed the alleles and genotypes of all research subjects using multivariate logistic regression analysis combined with 10,000 permutation tests. In addition, we also analyzed the distribution of haplotypes of the three SNPs in cervical cancer and cervical precancerous lesions. We found that the T allele and the dominant model of rs3093030 were associated with the susceptibility of cervical cancer (p = 0.042, p = 0.040, respectively). However, the significance disappeared after the Bonferroni correction for multiple testing (p > 0.05). For rs5498, its mutant gene G, the codominant model, and the dominant model could reduce the risk of CAC (p = 0.009, p = 0.028, p = 0.011, respectively). Significant differences remained after Bonferroni correction (p < 0.05, all). In addition, the frequency of haplotype “CTG” was significantly lower in the CAC group than in the controls. In conclusion, the study suggested that ICAM-1 gene polymorphisms may have a potential role in the pathogenesis of cervical cancer in the northern Chinese Han population.

The impact of ICAM-1, CCL2 and TGM2 gene polymorphisms on differentiation syndrome in acute promyelocytic leukemia

BackgroundAlthough arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are well-tolerated and effective treatments for Acute Promyelocytic Leukemia (APL), Differentiation Syndrome (DS) is a lethal side effect in some patients. The pathogenesis of DS is complex and not well understood; however, it is considered as an inflammatory response due to cytokines release of differentiated cells. Moreover, adhesion molecules that are widely expressed on the surface of differentiated cells and gene expression changes of transglutaminase2 (TGM2) are mechanisms involved in the development of DS. The purpose of this study was to assess the association of single nucleotide polymorphisms (SNP) of Intercellular Adhesion Molecule-1 (ICAM-1), chemokine (C-C motif) ligand 2 (CCL2) and TGM2 as inflammatory factors with differentiation syndrome susceptibility.MethodsDNA was extracted from 133 APL patients and 100 normal controls. Assessment according to the PETHEMA criteria revealed that 13.5% of these patients experienced differentiation syndrome. Tetra-ARMS PCR and PCR-RFLP were done to amplify DNA fragments in APL patients with and without DS. Then DNA sequencing was done to validate the results. SNPStats, SPSS and Finch TV were used to analyze the results.ResultsA significant correlation was found between rs4811528 in the TGM2 gene and differentiation syndrome susceptibility (P = 0.002, 95% CI = 1.74–18.81, OR = 5.72) while rs5498 in ICAM-1, rs1024611 in CCL2, and rs7270785 in TGM2 genes showed no correlation with differentiation syndrome. The G allele of rs7270785 and rs4811528 showed a haplotypic association with differentiation syndrome (P = 0.03, 95% CI = 1.13–13.86, OR = 3.96).ConclusionsAA genotype of the TGM2 SNP (rs4811528) may be a risk factor for development of DS in patients with APL following the use of ATRA/ATO.

Effects of 469 E/K polymorphism of ICAM1 gene in ischemic stroke and its association with stroke severity and outcome

Background: Stroke is the second leading cause of death globally and it is a major cause of long-term, physical, psychological, and social disability among the elderly. Increasing evidence shows that ischemic injury and inflammation account for its pathogenic progression. So, we studied the association of Intercellular Adhesion Molecule 1 (ICAM1) polymorphism with ischemic stroke, stroke severity, and outcome.&#x0D; Aims and Objectives: To compare ICAM1 469 E/K polymorphism in ischemic stroke patients with healthy controls, and to study its association with stroke severity and outcome.&#x0D; Materials and Methods: Fifty patients of ischemic stroke and hundred healthy individuals were included. The stroke severity was assessed clinically and radiologically. Outcome was measured at three and six months of stroke onset. Genomic DNA was used for Allele-Specific PCR to detect ICAM1 469 E/K polymorphism. The subjects were categorized into EE, EK, and KK genotypes.&#x0D; Results: The odds of EK genotype to develop stroke was 0.41 (95 % CI; 0.17 - 0.92) (p = 0.07) and of KK genotype was 0.41 (95 % CI; 0.11 - 0.87) (p = 0.04) compared to EE genotype. Subjects with ICAM1K allele had significantly reduced risk of stroke compared with those with E allele. (RR: 0.55; 95% CI: 0.35-0.87) (p=0.03).&#x0D; Conclusion: Subjects with ICAM1K allele had significantly reduced the risk of developing stroke. 469 E/K polymorphism of the ICAM1 gene does not significantly affect stroke severity, mortality, and outcome.

Association between K469E polymorphism of ICAM‐1 gene and susceptibility of ischemic stroke: An updated meta‐analysis

BackgroundThe intercellular adhesion molecule‐1 (ICAM‐1)/leukocyte function associated antigen‐1 (LFA‐1) adhesion system regulates leukocyte interactions, migration, and adhesion, and appears to play an important role in atherosclerosis and thrombosis. Therefore, single nucleotide polymorphisms (SNPs) of the ICAM‐1 gene may strongly influence the expression and biological activity of ICAM‐1 and play a potentially important role in the pathogenesis of ischemic stroke. In the current meta‐analysis, we investigated the relationship between the ICAM‐1 gene K469E SNP and the risk of ischemic stroke.MethodsTwo investigators independently searched PubMed, Web of Science, Google Scholar, WANFANG, China National Knowledge Infrastructure (CNKI) and J‐STAGE for studies published from January 2000 to February 2019 without language restriction. The association of K469E polymorphism and ischemic stroke in three genetic models (allelic, recessive, and dominant) were evaluated using Pooled odds ratios (ORs) with 95% confidence intervals (CIs).ResultsOur study included 20 studies from four continents and four different countries, including 3,137 cases and 15,382 controls. Meta‐analysis results did not show a significant association between K469E polymorphism of ICAM‐1 gene and ischemic stroke when assuming allelic model (OR: 1.12; 95% CI: 0.8 to 1.55; p = 0.51; I 2 = 93%) or recessive model (OR: 1.28; 95% CI: 0.89 to 1.84; p = 0.18; I 2 = 82%) or dominant model (OR: 1.20; 95% CI: 0.92 to 1.56; p = 0.17; I 2 = 85%). However, in all three genetic models, subgroup analysis revealed that the K469E polymorphism of the ICAM‐1 gene is associated with ischemic stroke in the Caucasian population.ConclusionK469E polymorphism of ICAM‐1 gene might be a risk factor for ischemic stroke in Caucasians, which suggested that K469E polymorphism might help in early identification of those at risk and help in primary prevention of ischemic stroke.

Association of MTHFR, IL-6 and ICAM-1 gene Polymorphisms with Coronary Artery Disease in South-Indian Ethnic Subset: A Case-Control Study

Introduction: Cardiovascular disease is the leading cause of mortality and morbidity all over the world. Among these cardiovascular deaths, half result from coronary artery disease (CAD). Increased prevalence of CAD is associated with increased levels of inflammatory markers. Phenotypic variations of these markers may depend on physiological stress or genetic variations. Materials and Methods: Single nucleotide polymorphism analysis of methylenetetrahydrofolate reductase (MTHFR), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) genes was done by PCR-DNA sequencing method. Results: Statistically significant elevation of inflammatory markers- homocysteine, hsCRP and fibrinogen were found in CAD group (p≤0.05). Multiple sequence alignment showed a single nucleotide mutation i.e., c.677 C>T (p. A222V) in exon-4 of MTHFR in 10% of CAD group and was associated with an increased risk of CAD (OR: 12.21). Mutations observed in exon-4 of IL-6 gene (in 26% of cases) was significantly associated with an increased risk of CAD (OR: 36.36). ICAM-1 (exon-6) mutation i.e., c.1405 A>G (p. K469E) was observed in 18% of patients and an increased risk of CAD (OR: 23.12). Conclusion: Polymorphisms observed in MTHFR, IL-6 and ICAM-1 genes in South- Indian ethnic population which are associated with elevated levels of inflammatory markers – homocysteine, hsCRP and fibrinogen appear to be predisposing factors for atherosclerosis.

Coexistence of IL-6 -572C/G and ICAM-1 K469E Polymorphisms among Patients with Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss (SSNHL) is a multifactorial disease, and its etiology remains elusive. SSNHL is possibly caused by both the environmental factors and genetic alterations. Recently, several studies suggested that inflammation may be involved in the pathogenesis of SSNHL, and certain gene polymorphisms may have correlations with SSNHL. Interleukin 6 (IL-6) functions both as a pro-inflammatory cytokine and an anti-inflammatory factor. Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin family that is also involved in inflammation response. Importantly, the IL-6 gene promoter contains a single nucleotide polymorphism (SNP), -572C/G, and ICAM-1 gene contains a SNP (A/G) in the protein-coding region, Lys (AAG)/Glu (GAG) at codon 469, known as K469E polymorphism. However, there is no study about the ICAM-1 gene polymorphism among SSNHL patients. In this study, we explored the relationship between SSNHL with IL-6 -572C/G and ICAM-1 K469E polymorphisms. We conducted a case-control study including 75 SSNHL patients and 165 healthy controls and analyzed the distribution and odds ratios of IL-6 and ICAM-1 genotypes. The frequency of the G allele at IL-6 -572C/G polymorphism was significantly higher among SSNHL patients than that among healthy individuals. In multivariate analysis, the coexistence of IL-6 -572G allele (GG/CG) and E allele (EE/KE) of ICAM-1 K469E polymorphism was significantly associated with an increased SSNHL risk (P < 0.001). In conclusion, we propose that the combination of IL-6 -572C/G and ICAM-1 K469E polymorphisms have a synergistic effect on the onset of SSNHL.

Correlations of ICAM-1 gene polymorphisms with susceptibility and multidrug resistance in colorectal cancer in a Chinese population.

Background:Colorectal cancer (CRC) is a malignant gastrointestinal tumor with a high mortality rate, including both colon and rectal cancer. In order to provide clinical guidance for the treatment of CRC, this study is conducted to investigate the correlations of intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms with susceptibility and multidrug resistance (MDR) of colorectal cancer (CRC).Methods:A total of 195 patients with CRC were selected as the observation group and 188 healthy people enrolled as the control group. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used to test ICAM-1 A13848G and K469E polymorphisms. The expressions of MDR-associated protein topoisomerase II (Topo II) and P-glycoprotein (P-gp) in CRC tissues were detected by immunohistochemistry. The analysis on association of clinical indexes of CRC patients with ICAM-1 gene polymorphisms was performed.Results:The frequencies of KK genotype and K allele of K469E in the observation group were significantly higher than that in the control group. KE + EE genotype and E allele might be protective factors for CRC. The distribution of genotypes, K469E KK and KE+EE, was highly correlated with histologic grade of tumor differentiation. Compared with adjacent normal tissues, positive rates of Topo II and P-gp expression were significantly increased in CRC tissues. Topo II expression in CRC patients was positively associated with lymph node metastasis and depth of tumor invasion, whereas P-gp expression was only associated with depth of tumor invasion. Higher positive rates of Topo II and P-gp expression were observed in ICAM-1 K469E KK genotype carriers, indicating that ICAM-1 K469E KK genotype might be related to MDR in CRC.Conclusion:These findings in the current study suggested that ICAM-1 K469E polymorphism is highly correlated with susceptibility and MDR in CRC.

Association of the intercellular adhesion molecule-1 gene polymorphisms with type 2 diabetes and diabetic peripheral neuropathy in a Chinese Han population

Intercellular adhesion molecule-1 (ICAM-1) is an inflammation cytokine. Previous studies have demonstrated that genetic polymorphisms in the ICAM-1 gene are associated with chronic inflammation and diabetic nephropathy. The present study aimed to investigate the association of ICAM-1 gene polymorphisms with type 2 diabetes (T2D) and diabetic peripheral neuropathy (DPN) in a Chinese Han population. Four valid single nucleotide polymorphisms (SNPs) in the ICAM-1 gene were genotyped in 672 control subjects, 787 T2D patients with and without DPN with TaqMan allelic discrimination. Single marker association analyses indicated that A allele of SNP rs5498 was associated with DPN (P = 0.037, OR 1.715, 95 % CI 1.027–2.865). Further analyses of clinical parameters according to the genotypes of this polymorphism demonstrated that T2D patients with DPN carrying AA and AG genotypes had higher risk of coronary heart disease compared with those carrying GG genotype (30.6 % vs. 11.5 %, P = 0.040). In SNP rs1799969, the difference of minor allele frequencies between the patients without and with DPN was found (0.02 vs 0.01, P = 0.014, OR 3.695, 95 % CI 1.211–11.277). SNP rs281432 had higher frequency of G allele in all T2D patients compared with control subjects (0.35 vs. 0.31, P = 0.041, OR 1.200, 95 % CI 1.008–1.428). The present study provides evidence that rs5498 (A/G E469K) polymorphism is associated with DPN in T2D, and also implicates that the association of ICAM-1 with DPN may be related to other vascular complications.

GW25-e3491 Association of Intercellular Adhesion Molecule-1 Gene Polymorphism with Coronary Heart Disease in Han population in Xinjiang, China

Intercellular adhesion molecule-1 is an important adhesion molecule that plays a crucial role in lymphocyte migration and in atherosclerosis pathogenesis activation. The aim of the present study was to explore the association between the rs5498 polymorphism of the ICAM-1 Gene and coronary heart

Association of intercellular adhesion molecule-1 gene polymorphism with coronary heart disease

Intercellular adhesion molecule‑1 (ICAM‑1) is an important adhesion molecule that has a crucial role in lymphocyte migration and atherosclerosis pathogenesis activation. The aim of the present study was to explore the association between the rs5498 polymorphism of the ICAM‑1 gene and coronary heart disease (CHD). The rs5498 polymorphism of the ICAM‑1 gene was detected using polymerase chain reaction‑restriction fragment length polymorphism in 674 patients with CHD and 779 control subjects. The results showed that the frequency of the G allele was significantly higher in patients with CHD than that in controls (29.1 vs. 23.3%; P<0.001). The frequency of the AG+GG genotypes was higher in patients with CHD than that in controls (49.7 vs. 40.8%; P=0.001). Multiple logistic regression analysis showed that AG+GG was an independent risk factor for CHD (odds ratio, 1.919; 95% confidence intervals, 1.471‑2.503; P<0.001). For males, the frequencies of the G allele and AG+GG genotype were also higher in patients with CHD than those in control subjects (frequency of G allele, 29.9 vs. 22.7%; P<0.001; frequency of AG+GG genotype, 50.6 vs. 40.3%; P=0.001). For females, no significant differences in genotype or allele distribution were observed between the two groups. In conclusion, it was demonstrated in the present study that the rs5498 polymorphism of the ICAM‑1 gene was associated with CHD in males. Males with the G allele (AG and GG genotype) may therefore have a higher risk for CHD than those with the AA genotype.

Effect of Proinflammatory Gene Polymorphisms on the Risk of Alzheimer's Disease

Background: A number of studies associate Alzheimer's disease (AD) with APOE polymorphism and alleles which favor the increased expression of immunological mediators such as cytokines or acute-phase proteins. Objective: In this study we evaluated the distribution of a set of functionally important polymorphisms of genes encoding prototypical inflammatory molecules in individuals with AD. We also investigated whether a synergistic effect of these proinflammatory gene polymorphisms on the risk of AD could be hypothesized. Methods: In a genetic association study that included 533 AD patients and 713 controls, the following gene polymorphisms were analyzed: C-reactive protein (CRP) 1059 G/C, interleukin 6 (IL6) -174 G/C, interleukin 1β (IL1B) -31 T/C, tumor necrosis factor α (TNF-α) -308 G/A, macrophage migration inhibitory factor (MIF) -173 G/C, monocyte chemoattractant protein 1 (CCL2) -2518 A/G, intercellular adhesion molecule 1 (ICAM1) 469 E/K, E-selectin (SELE) Ser128Arg, macrophage inflammatory protein 1α (CCL3) -906 T/A, matrix metalloproteinase 3 (MMP3) -1171 5A/6A and matrix metalloproteinase 9 (MMP9) -1562 C/T. Results: We found that IL6, IL1B, CCL2, CCL3, SELE, ICAM1, MMP3, and MMP9 gene polymorphisms were significantly and independently associated with AD. The association remained significant even after the Bonferroni correction. We also found that these proinflammatory polymorphisms were associated with different levels of risk for AD, depending on the number of high-risk genotypes concomitantly carried by a given individual. Conclusion: Proinflammatory genotypes might influence the development and progression of AD exerting a potential synergistic effect.

Prediction value of intercellular adhesion molecule-1 gene polymorphisms for epithelial ovarian cancer risk, clinical features, and prognosis

Intercellular adhesion molecule-1 (ICAM-1, encoded by ICAM-1) is implicated in tumorigenesis and tumor progression. ICAM-1 modulates the susceptibility to several types of cancer and the disease prognosis; however, its role in epithelial ovarian cancer (EOC) is unclear. Here, we evaluate single nucleotide polymorphisms (SNPs) in ICAM-1 as predictors of EOC risk and prognosis. Six ICAM-1 polymorphisms were genotyped in 408 patients with EOC and 520 controls using the MassARRAY system. The ICAM-1 mRNA levels in 89 EOC tissues and 35 normal ovarian tissues were examined using quantitative PCR. The ICAM-1 rs5498 G allele was associated with increased tumor grade (OR=2.650) and EOC risk (OR=1.405). This risk was more evident in females who had first-degree relatives (FDRs) with a tumor (OR=3.475) or who experienced early menarche (OR=2.774). The ICAM-1 expression in the cancerous tissue was elevated compared with that of normal ovarian tissues (p<0.0001), and it was associated with an rs5498 genotype (p=0.0002). ICAM-1 SNPs did not significantly predict the overall EOC survival (p>0.05). However, the rs5498 G allele correlated with EOC survival time in patients whose FDRs suffered from a tumor (p=0.001). ICAM-1 rs5498 likely confers a high risk for EOC in G allele carriers accompanied by up-regulation of ICAM-1 expression during carcinogenesis. The combination of ICAM-1 rs5498 and tumor history predicts the EOC prognosis.

Evaluation of the association between ICAM-1 gene polymorphisms and sICAM-1 serum levels in multiple sclerosis (MS) patients in Southeast Iran

Multiple sclerosis (MS) is an autoimmune nervous system disorder characterized by leukocytes recruitment into nervous system and demyelination. Intercellular adhesion molecule-1 (ICAM-1) mediates the extravasation of leukocytes and their accumulation in inflamed tissue. The aim of this study was to evaluate the probable association of ICAM-1 Exon 4 (G241R) and Exon 6 (E469K) gene polymorphisms with circulating levels of sICAM-1 in MS patients (n=78) and consecutive unrelated healthy controls (n=123). Analysis of ICAM-1 polymorphisms was performed by PCR with sequence-specific primers (SSP) and concentration of sICAM-1 in serum was performed by ELISA techniques. No significant differences were detected for allele frequencies of ICAM-1 Exon 4 and Exon 6 in MS patients than in the controls respectively (ns-P > 0.05). Moreover, baseline serum sICAM-1 concentrations to be significantly increased among patient carriers of K allele as compared with the respective non-carriers of these variants (P < 0.001). This study illustrates that K allele of the ICAM-1 codon 469 mutation might contribute to the pathogenesis of MS through increase levels of sICAM-1 and establish inflammation. Our result invites further investigation relevant to understanding the mechanisms underlying the immunopathogenesis of this autoimmune disease. Key words: Polymorphism, intercellular adhesion molecule-1, heterogeneity, single nucleotide polymorphisms (SNP).

K469E polymorphism of the intercellular adhesion molecule-1 gene in Egyptians with coronary heart disease

BACKGROUND AND OBJECTIVES:The initial step in atherosclerosis is the adhesion of leukocytes to activated endothelial cells mediated by intercellular adhesion molecule-1 (ICAM-1). This study aimed to investigate the association of K469E polymorphism of the ICAM-1 gene and soluble ICAM-1 (sICAM-1) serum level with coronary heart disease (CHD) in Egyptian subjects.PATIENTS AND METHODS:Using a case-control design, we studied 100 patients with CHD, including 73 patients with acute myocardial infarction (MI) and 27 with unstable angina (UA). The control group consisted of 50 healthy subjects with normal left ventricular function. All participants were genotyped for the ICAM-1 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serum sICAM-1 was measured by enzyme-linked immunoassay (ELISA).RESULTS:In CHD patients, the frequencies of K genotype (KK and EK) were significantly higher when compared to controls (P<.001) and were associated with an increased risk of disease development (OR=3.8, 95% CI: 1.7 to 8.5; P=.001). K genotype frequencies in patients with MI showed no significant difference when compared to patients with UA (P= .121). Serum sICAM-1 levels were comparable between CHD patients and controls (P= .37) and between MI and UA patients (P=.23). There were no significant differences in sICAM-1 levels among patients with different genotypes (P=.532). Men presented with higher sICAM-1 levels than women (P=.004).CONCLUSION:ICAM-1 gene polymorphism in codon 469 is associated with a risk for CHD development in Egyptian subjects. Serum sICAM-1 is not influenced by this polymorphism and is not necessarily elevated in CHD.

Intercellular adhesion molecule-1 gene polymorphisms in patients with familial mediterranean fever

Abstract Familial Mediterranean fever (FMF) is a disease of unknown etiology characterized by recurrent attacks of polyserositis and fever. Intercellular adhesion molecule-1 (ICAM-1) is known to contribute inflammatory conditions by regulating leukocyte localization at inflammatory sites. The aim of this study was to evaluate the probable association of ICAM-1 G/R 241 and ICAM-1 E/K 469 polymorphisms according to susceptibility with FMF. Sixty-seven FMF patients and 83 healthy volunteers were included in the study. Genomic DNA was extracted from EDTA-preserved whole blood of whole series of patients and controls, and genotyped by polymerase chain reaction (PCR) and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms G/R at codon 241 and E/K at codon 469. The ICAM-1 241 genotype and allele frequencies of FMF patients and healthy volunteers were similar. The frequency of ICAM-1 K469 homozygosity was significantly lower in FMF patients than in the controls (32.8% vs 50.7% subsequently, p=0.03). Moreover, ICAM-1 E469 allele was more frequent in FMF patients than in controls (44.8% vs 32.3%, p:0.03). Our results showed that ICAM-1 469 gene polymorphism could contribute to the pathogenesis of FMF.

Association between intercellular adhesion molecule-1 gene polymorphism and risk of colorectal cancer

Objective To investigate the association of single nucleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 ( ICAM-1) gene with the risk of colorectal cancer ( CRC). Methods Genotypes of ICAM-1 were analyzed by polymerase chain reaction-sequence specific primers (PCR-SSP) method among 87 cases of CRC specimens and 102 frequency-matched controls. Results The ICAM-1 -241G/R polymorphism was G/G genotype in all of CRC patients and controls, and R241 allele was not detected. The frequencies of the K/K, K/E and E/E genotypes in cases (57.47% , 33.18% and 10.35% ) were significantly different from those of controls (43.16% , 43.14% and 14.70% ). As compared with K/E + E/E genotypes, K/K genotype could significantly increase the risk of colorectal cancer (x2 =4.406, P 0.05). Conclusion There is no polymorphism of the ICAM-1-241 G/R in the population of North China. The K/K genotype and K allele significantly increase the risk of colorectal cancer occurrence. ICAM-1 -469K/E polymorphisms are associated with the degree of tumor differentiation. Key words: Colorectal carcinoma; Intercellular adhesion molecule-1; Single nucleotide polymorphisms

Intercellular adhesion molecule 1 K469E gene polymorphism is associated with presence of skin lesions in Tunisian Behçet's disease patients

Intercellular adhesion molecule 1 (ICAM1) gene polymorphisms have been implicated in the susceptibility to inflammatory diseases. The expression of both soluble and tissue ICAM1 were increased in Behçet's disease (BD) but the contribution of ICAM1 gene polymorphisms to this disease remains unknown. We sought to establish the association of ICAM1 gene K469E polymorphism in exon 6 with susceptibility for BD. One hundred and thirty-five Tunisian patients who satisfied the International Study Group criteria for BD and 157 healthy blood donor controls from the same geographic area were genotyped by polymerase chain reaction method for the K469E ICAM1 gene polymorphisms in exon 6. There were no significant differences in the distribution of the K469E allele or genotype frequencies between the BD patients and healthy controls in the ICA1 gene. Among patients, significant association was found between the presence of skin lesions and the studied polymorphism in the distribution of the K469E allele (P = 0.004; odds ratio = 1.26; 95% confidence interval = 2.13-3.62) and genotype frequencies (P = 0.0028; chi(2) = 11.75). Our findings suggest that K469E ICAM1 gene polymorphism was associated with Tunisian BD patients with skin lesions.