Intercellular Adhesion Molecule-1 K469E Research Articles

Significance of Intercellular adhesion molecule-1 Lys496Glu gene polimorphism on plasma redox status regulation in laryngeal carcinoma.

Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The present research is conducted to investigate whether specific gene polymorphism of ICAM-1 K469E (rs5498) and plasma redox status could be associated with laryngeal cancer (LC) development. Since there is no clear evidence which investigates the relationship between ICAM-1 polymorphism and ROS-mediated plasma protein oxidation in LC, our study is the first significant contribution for investigating the relationship. The study covered patients with primary LC and their age-matched healthy control subjects. Evaluation of ICAM-1 K469E (rs5498) gene polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. Plasma redox status was assessed with spectrophotometric methods. In the current paper, we found that LC patients with GG genotype had a decreasing trend for the plasma oxidative damage biomarker levels when compared with all allele genotypes (AA and AG). We concluded that G allele of the ICAM-1 K469E gene plays a significant role in the optimal regulation of plasma redox homeostasis in patients with LC.

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.

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.

P16 INTERCELLULAR ADHESION MOLECULE-1 K469E(A/G) POLYMORPHISM AND ITS EFFECTS IN THE DEVELOPMENT OF DIABETIC NEPHROPATHY

Recent research has implicated that inflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN), although its pathogenesis is multifactorial. Intercellular adhesion molecule 1 (ICAM-1) is an acute phase marker of inflammation and the ICAM-1 gene is located on chromosome 19p13.2 and resides a linkage region to diabetes and DN. To investigate whether ICAM-1 has effects in the development of DN, we have recently performed genetic and pathological studies of this molecule in Swedish and Malaysian subjects with normal glucose tolerance (NGT), diabetes and DN. We genotyped six single nucleotide polymorphisms (SNPs) in the ICAM-1 gene with TaqMan allelic discrimination. We also determined plasma ICAM-1 levels with an enzyme-linked immune-sorbent assay kit. We found that non-synonymous SNP rs5498 (K469E A/G) was associated diabetes and DN and the G allele had a protective effect. Particularly, we found a high heterozygous index of this polymorphism presenting in both populations. The genotype distribution of this polymorphism was kept in Hardy-Weinberg Equilibrium and no duplicon in the genomic sequence was found. The ICAM-1 K469E(A/G) polymorphism resides in the 5th Ig-like domain of ICAM-1 protein. This domain is essential for dimerization, surface presentation and solubilisation of proteins of the protein and subsequently plays a crucial role in the activity of ICAM-1 protein in the interaction with LFA-1 and the adhesion of B cells. Furthermore, we found the carriers with heterozygous genotype had higher fasting glucose levels among newly diagnosed type 2 diabetes patients compared with the subjects with wild or mutant homozygous genotype. Plasma ICAM-1 levels were increased from the subjects with NGT, diabetes without DN to the patients with DN. Among diabetic patients with DN, the carriers with heterozygous genotype had higher plasma ICAM-1 levels compared with other patients. Our study provided evidence that ICAM-1 has effects in the development of DN. The patients carrying with heterozygous genotype of SNP rs5498 (K469E A/G) in the ICAM-1 gene have higher risk susceptibility to DN. The combined approach with genotyping this polymorphism and measuring plasma ICAM-1 levels may be useful for prediction of DN in translation medicine.

Association of the intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms with endometriosis: a systematic review and meta-analysis.

Reported associations of the G241R and K469E polymorphisms of the intercellular adhesion molecule-1 gene (ICAM-1) gene with endometriosis have differed in magnitude. In a meta-analysis of six published case-control studies (from five articles), we estimated risk [odds ratio (OR) 95 % confidence intervals (CI)] of associations with these polymorphisms using the Review Manager 5.3 software. Based on 1213 cases and 1103 controls, overall analysis showed significant increased risk in the homozygous (OR 2.83, 95 % CI 0.99-8.10, p = 0.05), dominant (OR 1.86, 95 % CI 1.00-3.46, p = 0.05) and codominant (OR 2.15, 95 % CI 1.06-4.35, p = 0.03) models. Confined to the studies in Hardy-Weinberg Equilibrium erased the significance (OR 1.59-2.59, 95 % CI 0.81-8.22, p = 0.10-0.15). Asian effects were variable (OR 0.93-1.09, p = 0.50-0.57), but Caucasian effects were not (OR 4.09-13.60, p < 0.0001). Independent data for the late stages of endometriosis suggest protection of the ICAM-1 K469E polymorphism among the Asians (OR 0.91-0.95, p = 0.35-0.71). These effects were weak but non-heterogeneous (P heterogeneity = 0.17-0.57, I (2) = 0-40 %). In summary, strengths of the overall effects were consistency, significance and robustness but limited by their high heterogeneity. These strengths and limitations were also observed in the Caucasian subgroup which when tested for interaction against the contrasting Asian effects, highlighted Caucasian susceptibility (p = 0.004-0.01). The findings are an interplay of strengths and limitations, which warrant awareness of their interpretation as susceptibility markers for this disorder.

The ICAM-1 K469E polymorphism is associated with the risk of coronary artery disease: a meta-analysis.

The intercellular adhesion molecule-1 (ICAM-1) K469E polymorphism has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but the results of studies are still debatable. Thus, a meta-analysis was carried out. Databases including PubMed, Embase, Web of Science, and CNKI were searched. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Eighteen studies with 3546 cases and 3852 controls were included in this meta-analysis. The association between the ICAM-1 K469E polymorphism and the risk of CAD was significant (OR=1.77; 95% CI, 1.52-2.05; P<0.01; I=27%). This result remained statistically significant when the adjusted ORs were combined (OR=1.95; 95% CI, 1.78-2.14; P<0.01; I=0%). When stratified by ethnicity, a significantly increased risk was observed in Whites (OR=1.75; 95% CI, 1.37-2.23; P<0.01; I=58%) and in Asians (OR=1.80; 95% CI, 1.45-2.24; P<0.01; I=0%). A significantly increased risk of myocardial infarction was observed (OR=2.24; 95% CI, 1.72-2.92; P<0.01; I=38%). In conclusion, this meta-analysis suggested that the ICAM-1 K469E polymorphism was a risk factor for CAD.

Associations of a polymorphism in the intercellular adhesion molecule-1 (ICAM1) gene and ICAM1 serum levels with migraine in a Chinese Han population

ObjectiveTo investigate the associations of a polymorphism in the intercellular adhesion molecule-1 (ICAM1) gene, and ICAM1 serum levels, with migraine and migraine subtypes in a Han Chinese population. MethodWe used PCR-restriction fragment length polymorphism (PCR–RFLP) and gene sequencing to analyze the genotype and allelic frequencies of the K469E (rs5498) and G241R (rs1799969) ICAM1 polymorphisms between migraine cases and controls. Serum levels of ICAM1 were tested by enzyme linked immunosorbent assay (ELISA). Results(1) We found significant higher frequencies of the distribution of the E/E genotype and the E allele of the K469E polymorphism between migraine cases and controls (χ2=4.948 &P<0.05 and χ2=13.990 &P<0.01, respectively), and between a migraine without aura subtype of migraine cases and controls (χ2=5.265 &P<0.05; χ2=20.501 &P<0.01, respectively). After correction by conditional logistical regression, the frequency distribution difference of the E/E genotype between the migraine cases and controls remained statistically significant (OR=32.85, 95% CI:4.22–28.79, P=0.007.) (2) ICAM1 serum levels were significantly higher in migraine cases than in controls (P<0.01) and, within migraine cases, were significantly higher in K469E E allele carriers than in K allele carriers (P<0.01). ConclusionsOur data indicate that the E/E genotype of the ICAM1 K469E polymorphism may be an important risk factor for migraine in a Han Chinese population, and that this polymorphism affects ICAM1 serum levels. Although the independent risk factor constituted by this polymorphism in other ethnic groups requires further study, our studies raise the possibility of the development of ICAM1 K469E E allele-specific therapeutics for the prevention and treatment of migraine in the Chinese Han population.

Role of ICAM-1 polymorphisms (G241R, K469E) in mediating its single-molecule binding ability: Atomic force microscopy measurements on living cells

Atherosclerosis (As) is characterized by chronic inflammation and is a major cause of human mortality. ICAM-1-mediated adhesion of leukocytes in vessel walls plays an important role in the pathogenesis of atherosclerosis. Two single nucleotide polymorphisms (SNPs) of human intercellular adhesion molecule-1 (ICAM-1), G241R and K469E, are associated with a number of inflammatory diseases. SNP induced changes in ICAM-1 function rely not only on the expression level but also on the single-molecule binding ability which may be affected by single molecule conformation variations such as protein splicing and folding. Previous studies have shown associations between G241R/K469E polymorphisms and ICAM-1 gene expression. Nevertheless, few studies have been done that focus on the single-molecule forces of the above SNPs and their ligands.In the current study, we evaluated both single molecule binding ability and expression level of 4 ICAM-1 mutations – GK (G241/K469), GE (G241/E469), RK (R241/K469) and RE (R241/E469). No difference in adhesion ability was observed via cell adhesion assay or atomic force microscopy (AFM) measurement when comparing the GK, GE, RK, or RE genotypes of ICAM-1 to each other. On the other hand, flow cytometry suggested that there was significantly higher expression of GE genotype of ICAM-1 on transfected CHO cells. Thus, we concluded that genetic susceptibility to diseases related to ICAM-1 polymorphisms, G241R or K469E, might be due to the different expressions of ICAM-1 variants rather than to the single-molecule binding ability of ICAM-1.

Investigation of ICAM-1 and β3 Integrin Gene Variations in Patients with Brain Tumors

Primary brain tumors constitute a small percent of all malignant cancers, but their etiology remains poorly understood. β3 integrin (ITGB3) has been recognized to play influential roles in angiogenesis, tumor growth and metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be associated with brain cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between brain tumor risk and ICAM-1 and β3 integrin gene polymorphisms. The study covered 92 patients with primary brain tumors and 92 age-matched healthy control subjects. Evaluation of β3 integrin (Leu33Pro (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to results of our research, the A allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele of ICAM-1 R241G was statistically significant in patients with brain tumors classified as glioma (p<0.001). When allele and genotype distributions of ICAM- 1 K469E, ICAM-1 R241G and β3 integrin Leu33Pro gene polymorphisms were evaluated with age, sex, and smoking, there were no statistically significant differences. Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918) and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients as compared with controls (p=0.001; p=0.036 respectively). This study provides the first evidence that ICAM-1 R241G SNP significantly contributes to the risk of primary brain tumors in a Turkish population. In addition, our results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective effects against the development of brain cancer.

Association between intercellular adhesion molecule-1 K469E polymorphism and coronary heart disease in people with Uygur ethnicity, in Xinjiang

To explore the distribution on K469E single nucleotide polymorphism of ICAM-1 gene among people with Uygur ethnicity, in Xinjiang and to analyze the correlation between ICAM-1 gene polymorphism and coronary heart disease. 245 patients with coronary heart disease patients and 377 healthy controls in Xinjiang Uygur population were studied. ICAM-1 gene K469E genotype located in exon 6 were detected by polymerase chain reaction-restricted fragments length polymorphism. Distribution of genotypes in the two groups appeared to be in Hardy-Weinberg equilibrium (P > 0.05). The distribution of genotypes showed significant difference between the two groups (P = 0.039)and the distributions of K and E allele also presented statistically significant difference (P = 0.031). Significant difference was also observed in males(P = 0.029 for genotype, P = 0.025 for allele)but not in females. After adjusted for confounding factors, results from logistic regression analysis indicated that KK genotype was a risk factor for CHD in Uygur male population (OR = 2.389, 95% CI:1.458-3.915, P = 0.001). Genetic polymorphism of ICAM-1 K469E might increase the risk for coronary artery disease in males of Uygur patients in Xinjiang.

ICAM1 K469E and E-selectin S128R polymorphisms could predispose to increased autoantibody production and TSH suppression in Graves’ disease

The etiopathogenesis of Graves' disease (GD) has not been clearly elucidated although the role of chronical inflammation and endothelial dysfunction has been established. Adhesion molecules such as intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and E-selectin are secreted from vascular endothelium and promote accumulation of leukocytes in damaged endothelial areas. This study examined the possible association of ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) single nucleotide polymorphisms (SNPs) with the occurrence of GD. ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs in DNA from peripheral blood leukocytes of 171 patients with GD and 259 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes. We did not find significant differences in the distributions of studied polymorphisms, nor in the haplotype frequencies between patients with GD and healthy control. However, the anti-TPO levels in E-selectin 128R allele carrying subjects (SR + RR) were higher than S128S genotype (p < 0.05). In addition, the decline of TSH levels was more prominent in ICAM1 469 E carrying subjects (KE + EE) in comparison with wild homozygotes (p < 0.05). Although there is not association between ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs and susceptibility to GD, higher anti-TPO in E-selectin 128 SR + RR, and lower TSH in ICAM1 469 KE + EE subjects suspect that these genotypes are prone to increased antithyroid autoantibody production with more accentuated TSH suppression in GD. Further studies with a larger cohort, analyzing other polymorphisms in ICAM, VCAM1 and E-selectin genes are necessary to support our observations.

G241R and K469E polymorphisms of intercellular adhesion molecule 1 (ICAM-1) could predispose to Hashimoto thyroiditis

This study examined firstly the possible association of G241R and K469E single nucleotide polymorphisms (SNPs) of ICAM-1 gene with the occurrence of Hashimoto thyroiditis (HT). G241R and K469E SNPs in DNA from peripheral blood leukocytes of 190 HT and 247 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes. There was a significant increase of ICAM-1 241R allele frequency in patients with HT compared with healthy controls (P = 0.04, OR = 1.84, 95 % CI = 1.00-3.37). Regarding ICAM-1 K469E polymorphism, patients homozygous for E allele had 1.73-fold increased risk for developing HT according to KK homozygotes (P = 0.04, 95 % CI = 1.00-3.01). The 469E allele frequency was higher in HT patients according to controls, however the difference was at borderline significance (P = 0.05, OR = 1.30, 95 % CI = 1.00-1.70). No associations between polymorphisms and HT phenotypes were observed. We suggest that the G241R and K469E SNPs of ICAM-1 gene may be related to occurrence of HT. However, more studies with larger sample size including other loci of the ICAM-1 gene are necessary to support our findings before any definite statement can be made about the relationship between HT and ICAM-1 polymorphism.

The intercellular adhesion molecule-1 (ICAM-1) gene polymorphism K469E in end-stage renal disease patients with cardiovascular disease

The intercellular adhesion molecule-1 (ICAM-1) mediates interaction of activated endothelial cells with leukocytes. It plays an important role in the pathogenesis of atherosclerosis. A functionally important polymorphism of the ICAM-1 gene, K469E, has been described. We investigated whether this polymorphism influences the risk of CVD in end-stage renal disease (ESRD) patients. The groups of 1016 ESRD patients and 824 healthy individuals were genotyped by PCR and allele specific oligonucleotide technique. The T allele of the K469E polymorphism was significantly more frequent in ESRD CVD+ patients than CVD- and controls (OR 2.26, 95% CI 1.87-2.72 and 1.82, 95% CI 1.55-2.11, respectively). The TT genotype was also more frequent in CVD+ patients (OR 9.90, 95% CI 6.17-15.88 vs. CVD- subgroup). When patients were stratified according to clinical outcome of CVD, there was a tendency towards higher frequencies of the T allele and TT genotype in patients with myocardial infarction (OR for T allele 1, 57, 95% CI 1.12-2.18 vs. patients without MI). In the multivariate regression analysis the carrier status of T allele of K469E was an independent risk factor of susceptibility to CVD. Our data suggest that the ICAM-1 K469E polymorphism is associated with CVD in ESRD patients.

ICAM-1 K469E polymorphism is a genetic determinant for the clinical risk factors of T2D subjects with retinopathy in Indians: a population-based case–control study

ObjectiveElevated levels of intercellular adhesion molecule-1 (ICAM-1) are demonstrated in diabetes complications. The current study aims to understand association of K469E (rs5498) in ICAM-1 gene, in type 2 diabetic (T2D)...

Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis

To investigate the association between single nucleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk, biological behavior and prognosis of gastric cancer (GC) in Chinese population. The study group consisted of 332 GC patients and 380 healthy controls. Genotyping was performed using polymerase chain reaction and the results were confirmed by sequencing. The association of ICAM-1 K469E polymorphisms and the risk of GC were studied, and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was analyzed. Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios: 1.36; 95% confidence interval (CI): 1.01-1.84; P = 0.041]. GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%, respectively; P = 0.002). In addition, patients at stage IV had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%, respectively; P = 0.046). Follow-up study showed that the overall cumulative survival rate was 23.7% in AA genotype group and 42.9% in AG and GG genotypes group. In univariate analysis, AA genotype was correlated with the overall cumulative survival (P = 0.034). But in multivariate analysis, ICAM-1 polymorphism was not an independent prognostic factor for the overall survival (relative risk, 1.145; 95% CI: 0.851-1.540; P = 0.370). Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC, predicting disease progression, and guiding individualized treatment.

Intercellular Adhesion Molecule-1 and Interleukin-6 Gene Polymorphisms in Patients with Advanced-Stage Endometriosis

Background/Aims: The aim of this study was to investigate the possibility that the K469E and G241R polymorphisms in the intercellular adhesion molecule-1 (ICAM-1) gene and the C-634G polymorphism in the interleukin (IL)-6 gene are associated with endometriosis in the Korean population. Methods: The ICAM-1 gene K469E and G241R polymorphisms and the IL-6 gene C-634G polymorphism were evaluated in 390 patients with endometriosis and 351 controls by polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The ICAM-1 gene G241R polymorphism was not observed in all subjects. No differences were observed in the ICAM-1 K469E and IL-6 C-634G genotype distributions and allele frequencies between patients with endometriosis and controls. In subgroup analyses according to the stage of endometriosis or bilaterality of ovarian endometriomas, no significant differences were observed in the ICAM-1 gene K469E or the IL-6 gene C-634G polymorphism frequencies between the subgroups and the controls. The combined analysis of the ICAM-1 gene K469E polymorphism and the IL-6 gene C-634G polymorphism did not show any additional significant findings. Conclusions: The K469E and G241R polymorphisms in the ICAM-1 gene and the C-634G polymorphism in the IL-6 gene may not be genetic factors related to susceptibility to advanced-stage endometriosis in the Korean population.

Intercellular adhesion molecule-1 gene K469E polymorphism and ischemic stroke: a case-control study in a Chinese population

Intercellular adhesion molecule-1 (ICAM-1) was involved in the pathogenetic mechanisms responsible for ischemic stroke (IS). Population-based sample have revealed gene-gender interaction in blood pressure which is major risk for IS. We sought to evaluate whether ICAM-1 K469E polymorphism was involved in the causation of IS and whether it was different between female and male. A 1:1 case-control study was conducted. The K469E polymorphism of ICAM-1 gene were analyzed by polymerase chain reaction (PCR) and restriction enzyme analysis in Chinese patients with IS (n = 309) and elderly subjects without IS (n = 309). ICAM-1 K469E polymorphism was significantly associated with IS. Interestingly, a further analysis stratified by sex found that there was significance between 469E genotypes and IS in female, but not in male. Multiple regression analysis revealed that ICAM-1 K469E polymorphism was still significantly associated with IS, compared with ICAM-1 KK genotype in all population (OR = 1.60, P = 0.030). Stratified by sex, EE combined EK was contributory factor to IS in female (OR = 3.03, P = 0.004), but not in male. After adjustment for confounding factors, the interaction between female and ICAM-1 EK/EE genotypes was found (OR = 3.54, P = 0.001). It is suggested that the ICAM-1 469E allele may be important in the pathogenesis of ischemic stroke, especially in female but not in male.

Susceptibility to active decompensated cirrhosis is associated with polymorphisms of intercellular adhesion molecule‐1 (ICAM‐1) in chronic HBV carriers

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the pathogenesis of viral hepatitis B. Several inflammatory diseases are associated with distinct polymorphisms of the ICAM-1 gene. The aims of this study were to analyse the association of ICAM-1 polymorphisms G241R and K469E with susceptibility to active decompensated cirrhosis in chronic hepatitis B virus (HBV) carriers. The polymorphisms at codons G241R and K469E of ICAM-1 were analysed by sequence-specific primer polymerase chain reaction (PCR-SSP) in 572 unrelated chronic HBV carriers and 157 unrelated healthy HBV non-infected blood donors. There were significantly increased frequencies of R at codon 241 and E at codon 469 in patients with active decompensated cirrhosis (38.3% and 58.3%), compared with patients with chronic hepatitis B (CHB; 21.9% and 46.5%) and chronic asymptomatic HBV carriers (AsC; 12.6% and 40.3%). The frequencies of R241-E469 haplotype and genotypes carrying at least one R241-E469 haplotype were significantly higher in patients with active decompensated cirrhosis than those in patients with CHB (38.3% and 63.3%vs 21.9% and 36.7%), and significantly higher in patients with CHB than those in AsC (21.9% and 36.7%vs 12.6% and 23.3%). The ICAM-1 polymorphisms at codons G241R and E469K were associated with the disease susceptibility, and susceptibility to active decompensated cirrhosis is significantly increased in chronic HBV carriers carrying at least one R241-E469 haplotype.

Rapid detection of intercellular adhesion molecule 1 (G241R and K469E) polymorphisms by a novel PCR–SSP assay

Intercellular adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein member of the immunoglobulin superfamily and is actively involved in immune and inflammatory responses. We introduce a novel polymerase chain reaction-sequence-specific primers (PCR-SSP) method for rapid and simultaneous genotyping of ICAM-1 G241R and K469E polymorphisms. In a total of 184 DNA samples that have been previously analyzed for these polymorphisms using polymerase chain reaction-restriction fragment length polymorphism technique, re-genotyping of all samples with this new assay showed accurate and reproducible results. As PCR-SSP-based genotyping protocols are more convenient and cost-effective to do, it could therefore offer a valuable tool for assessment of ICAM-1 polymorphisms to which more confirmatory studies are needed.