Intercellular Adhesion Molecule-1 Gene K469E Research Articles

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.

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 between the ICAM-1 gene polymorphism and coronary heart disease risk: a meta-analysis

Coronary heart disease (CHD) is a complex polygenic disease in which gene-environment interactions play a critical role in disease onset and progression. The Intercellular adhesion molecule 1 (ICAM-1) gene E469K polymorphism is one of the most commonly studied polymorphisms in this gene because of its association with CHD risks, but results were conflicting. The PubMed, Embase, and China National Knowledge Infrastructure databases were searched for case–control studies published up to November 2018. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the association. Eleven eligible studies, comprising 3435 cases and 3199 controls, were included in the meta-analysis. The pooled result showed that the ICAM-1 gene E469K polymorphism was significantly associated with an increased risk of CHD (OR = 1.20, 95% CI = 1.11–1.29, for the allele K versus allele E; OR = 1.66, 95% CI = 1.43–1.92, for the K allele carriers versus EE). Subgroup analysis supported the results in the Chinese populations and in the Caucasian populations. This meta-analysis suggests that the ICAM-1 gene K469E polymorphism is associated with CHD risk and the K allele is a more significant risk factor for developing CHD amongst Chinese and Caucasians populations.

Meta-analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes.

To collectively evaluate the association of intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism (rs5498) with diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM). Overall review of available literatures relating K469E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios (ORs). Potential sources of heterogeneity and bias were explored. Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469E polymorphism with DR (P>0.05). A statistically significant association was detected between the K469E polymorphism and proliferative diabetic retinopathy (PDR) in Asians only in dominant model (GG+AG vs AA) with pooled OR of 0.729 (95%CI: 0.564-0.942, P=0.016, P heterogeneity=0.143), however, this association was not detected in recessive model (GA+AA vs GG; OR=1.178, 95%CI: 0.898-1.545, P=0.236, P heterogeneity=0.248) or allelic model (G vs A; OR=0.769, 95% CI: 0.576-1.026, P=0.074, P heterogeneity=0.094). No publication bias was found by Funnel plot, Begg's and Egger's test. This research found no statistically significant association between ICAM-1 gene K469E polymorphism and DR in patients with T2DM, but showed significant association of the K469E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion.

Association between intercellular adhesion molecule-1 gene K469E polymorphism and the risk of stroke in a Chinese population: a meta-analysis

Several epidemiologic studies have evaluated the association between intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism and stroke, but the results were inconsistent. The present meta-analysis was performed to investigate the relationship between K469E polymorphism and stroke in the Chinese population. A comprehensive search for related studies from the electronic databases of PubMed, Embase, Web of Science, CBMdisc and CNKI as well as a manual search of the references of identified articles was performed. Data were extracted to calculate for allelic, additive, dominant and recessive models using pooled odds ratios (ORs) along with 95% confidence intervals (CIs) by Review Manager 5.0 and Stata 11.0. Different effect models, subgroup analysis, sensitivity analysis, publication bias and power calculations were used to improve the comprehensive analysis. Finally, a total of 12 studies containing 1593 cases and 1555 controls were included in the final meta-analysis. No evidence of significant association between ICAM-1 gene K469E polymorphism and stroke was found in all four models (allelic model: OR = 1.07, 95%CI = 0.78–1.47; additive model: OR = 1.21, 95% CI = 0.67–2.16 (EE vs. KK); OR = 1.04, 95%CI = 0.75–1.45 (EK vs. KK); dominant model: OR = 1.07, 95% CI = 0.73–1.56; and recessive model: OR = 1.18, 95% CI = 0.77–1.83, respectively) based on the overall population, as well as subgroup analysis and sensitivity analysis. In conclusion, the present meta-analysis showed no evidence of significant association between ICAM-1 gene K469E polymorphism and stroke in the Chinese population. Nonetheless, this conclusion should be interpreted cautiously due to the low statistical power and considerable heterogeneity. Therefore, larger sample-size studies with homogeneous cases and well-matched controls are needed to further address this correlation.

KE and EE Genotypes of ICAM-1 Gene K469E Polymorphism Is Associated with Severe Preeclampsia

Background. Preeclampsia (PE) is one of the most important complications of pregnancy that is associated with significant mortality and morbidity in mother and fetus. Since the etiologic factors in its development are still unclear, we aimed to examine the intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism in preeclamptic and control healthy women. Materials and Methods. Genetic polymorphism was analyzed in 192 PE and 186 healthy control women. PCR-RFLP method was used to identify K469E polymorphism. Results. The frequency of KK, KE, and EE genotypes of ICAM-1 gene was not different between PE patients and healthy pregnant women. Whereas, the frequency of KE and EE genotypes was significantly higher in severe PE than mild PE women and control group, and the risk of severe PE was 2.4-fold higher in subjects with KE genotype (OR, 2.4 [95% CI, 1 to 5.9]; P = 0.03) and 3.3-fold higher in subjects with EE genotype (OR, 3.3 [95% CI, 1.2 to 9]; P = 0.015) compared to individuals with KK genotype. Conclusion. We concluded that KE and EE genotypes of K469E polymorphism could increase risk of severe PE.

Association of intercellular adhesion molecule-1 gene K469E polymorphism with chronic obstructive pulmonary disease

To test the association of K469E, the common intercellular adhesion molecule-1 (ICAM-1) polymorphism with chronic obstructive pulmonary disease (COPD) and expression of ICAM-1 in Han people of Central and South Region in China. A case-control study was done on 91 patients with COPD and 80 matched controls of Han people from central and south region in China, mainly from Hunan Province. Genomic DNA was extracted from white blood cells. ICAM-1 sequences were amplified by PCRand analyzed by agarose gel electrophoresis. Genotypes were defined by base sequencing. In addition, soluable intercellular adhesion molecule-1 (sICAM-1) serum levels were measured in 86 people picked out randomly from the COPD group and the control group. There was no difference in the frequency of the genotype and allele between the COPD group and the controls, but compared with those who were not very severe, the frequency of KE/ EE genotypes and E allele in COPD patients at very severe stage was significantly higher (10/16 vs 26/75, 12/30 vs 20/150, P<0.05). The level of sICAM-1 increased in the COPD patients, with negative correlation to forced expiratory volume in one second for the percentage of predicted value (FEV1%). But in both COPD patients and controls, the level of sICAM-1 did not differ significantly in different genotypes(P>0.05). K469E polymorphism of ICAM-1 may not affect the susceptibility of COPD and the expression of ICAM-1 in Han people from central and south of China in this study, but carriers of E allele are at high risk of developing severe stage of COPD.

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 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.

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.

Association of intercellular adhesion molecule 1 polymorphisms with retinopathy in Chinese patients with Type 2 diabetes

To investigate the relationship of the K469E and G241R polymorphisms of the intercellular adhesion molecule 1 (ICAM-1) gene with diabetic retinopathy in Chinese patients with Type 2 diabetes mellitus. One hundred and seventy-two Chinese patients with Type 2 diabetes and 80 normal control subjects were recruited. Patients with diabetes were placed into two groups: the diabetic retinopathy (DR) group and the non-diabetic retinopathy (NDR) group. The DR group was subdivided into those with proliferative retinopathy (PDR) and non-proliferative retinopathy (NPDR). Genomic DNA was prepared using the hydroxybenzene-chloroform extraction method. Genotypes and alleles were detected by polymerase chain reaction-heteroduplex-single-strand conformation polymorphism (PCR-HA-SSCP) analysis combined with gene sequencing. The patients with retinopathy had an increased frequency of the K469K genotype compared with both the patients without retinopathy and the control subjects (61.4 vs. 40.0 and 35.0%, respectively; chi(2) = 8.280 and 13.952, respectively; P < 0.05). The frequency of the K allele in the DR group was higher than in the NDR group and control subjects (75.4 vs. 58.8 and 61.3%, respectively; chi(2) = 9.693 and 11.219, respectively; P < 0.05). Genotype and allele frequencies were similar in the NDR group and control subjects, and in the PDR and NPDR groups. The ICAM-1 gene K469E polymorphism is associated with diabetic retinopathy in Chinese patients with Type 2 diabetes. Patients with the K469K genotype were more likely to have diabetic retinopathy than patients with the K469E or E469E genotype.