Intercellular Adhesion Molecule-1 K469E Polymorphism Research Articles

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.

Intercellular adhesion molecule-1 K469E polymorphism and risk of coronary artery disease: a meta-analysis.

BackgroundIntercellular adhesion molecule-1 (ICAM-1) K469E polymorphism has been implicated in susceptibility to coronary artery disease (CAD). Several studies investigated the association of this polymorphism with CAD in different populations but the results were contradictory. A meta-analysis was conducted to assess the association between ICAM-1 K469E polymorphism and CAD susceptibility.Material/MethodsDatabases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A random-effects model was used.ResultsFifteen case-control studies including 3088 cases and 3466 controls were included. Overall, a significant association between ICAM-1 K469E polymorphism and CAD was observed in the dominant model (OR=1.80; 95% CI 1.62–2.01; P<0.00001; Pheterogeneity=0.40). In subgroup analysis by ethnicity, a significant association was found among Asians (OR=1.92; 95% CI 1.51–2.43; P<0.00001; Pheterogeneity=0.98) and among Caucasians (OR=1.64; 95% CI 1.30–2.08; P<0.0001; Pheterogeneity=0.04). In the subgroup analysis by age, a significant association was found among young patients (OR=1.46; 95% CI 1.10–1.93; P=0.008; Pheterogeneity=0.21) and old patients (OR=1.92; 95% CI 1.75–2.10; P<0.00001; Pheterogeneity=0.99).ConclusionsResults of this meta-analysis suggest that ICAM-1 K469E polymorphism confers a risk factor of CAD.

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 K469E polymorphism in Korean patients with spontaneous preterm delivery

Objectives To investigate the association between intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism and spontaneous preterm delivery in a Korean population. Methods Genomic DNA was extracted from whole blood from 55 women experiencing preterm labor and 153 multiparous women (control group) with a history of at least 2 term deliveries. DNA samples were analyzed by polymerase chain reaction–restriction fragment length polymorphism. Results The spontaneous preterm delivery (SPD) group carried the 469E allele significantly more frequently than those in the control group (odds ratio [OR], 1.62; 95% CI, 1.04–2.53). The EE genotype was significantly associated with increased risk of SPD (OR, 2.84; 95% CI, 1.17–6.89; P = 0.02). Allelic frequencies in women with abnormal C-reactive protein levels (K = 0.48; E = 0.52) were significantly different from frequencies in the controls (K = 0.68; E = 0.32) ( P = 0.006). Conclusions ICAM-1 gene K469E polymorphism may be a candidate region and useful predictor of susceptibility to SPD 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.

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.

Association Study of Endometriosis and Intercellular Adhesion Molecule-1 (ICAM-1) Gene Polymorphisms in a Japanese Population

Endometriosis is an immune-related, chronic inflammatory disease with polygenic predisposition. Cell adhesion molecules are expressed in endometriotic lesions, and in cells and tissues that are involved in the development and progression of the disease. In this study, we investigated the possible association between endometriosis and the G241R and K469E polymorphisms in the intercellular adhesion molecule-1 (ICAM-1) gene in a Japanese population. We compared the distribution of the G241R and K469E polymorphisms in the ICAM-1 gene in 126 endometriosis patients and 172 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in a Japanese population. There were no significant differences between the cases and controls in the allele frequencies or genotype distributions of either the G241R or K469E polymorphisms in the ICAM-1 gene. The endometriosis patients were divided into a subgroup of women with severe disease only. However, no significant differences were observed in the allele frequencies and genotype distributions of the ICAM-1 K469E polymorphisms between this subgroup and the controls. In contrast, only one in 169 controls was heterozygous (G/A genotype), and the A allele in the G241R polymorphism was not found in any of the 126 endometriosis patients. Our findings suggest that the G241R and K469E polymorphisms in the ICAM-1 gene are unlikely to be associated with an increased risk of endometriosis in the Japanese population.

The intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism is not associated with ischaemic heart disease: an investigation using family-based tests of association.

The possible role of the K469E polymorphism in the intercellular adhesion molecule-1 (ICAM-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family-based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the ICAM-1 K469E polymorphism. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the ICAM-1 K469E polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the ICAM-1 K469E polymorphism is not associated with IHD.

Intercellular adhesion molecule-1 polymorphisms in Korean patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by synovial proliferation and the accumulation of inflammatory cells in the affected joints. Intercellular adhesion molecule-1 (ICAM-1) is readily detected in RA synovial tissues and helps recruit inflammatory cells to the joint. ICAM-1 shows genetic polymorphisms at codons 241 (R241G) and 469 (K469E). In order to investigate the association between ICAM-1 gene polymorphisms and RA, we genotyped ICAM-1 R241G and ICAM-1 K469E polymorphisms in 143 Korean patients with RA, and in 138 healthy controls, by using the polymerase chain reaction-restriction fragment length polymorphism method. No polymorphism of R241G was found in Korean subjects. However, the frequency of the K469 allele was found to be significantly lower in RA patients than in healthy controls. Allele frequency of K469 was lower in RA patient group, compared to that in healthy controls, regardless of the shared epitope status. Distribution of K469E allele frequencies was not different whether the patient had rheumatoid factor, radiographic erosion or extra-articular complications. In conclusion, this study shows lower frequency of the ICAM-1 K469E allele in Korean patients with RA than that in healthy controls.

Intercellular adhesion molecule-1 K469E polymorphism: study of association with multiple sclerosis

Intercellular adhesion molecule-1 (ICAM-1) is involved in the pathogenesis of multiple sclerosis (MS), whereas sequence variations in the ICAM-1 gene could potentially be responsible for the genetic susceptibility to MS. We studied an association of MS with the 13,848A>G (K469E) polymorphism of the ICAM-1 gene in Finnish and Spanish cases and controls and affected families. An increased risk for the AA (Lys 469/Lys 469) genotype was found in both populations. The effect observed was found to be strongest among the HLA-DQB1*0602–positive subjects, which implies genetic heterogeneity of MS. Meta-analysis of all published datasets supports increased risk of MS for the ICAM-1 Lys 469 homozygotes (relative risk = 1.3, p = 0.002).