Dataset Information

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

ABSTRACT: BACKGROUND:The 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. METHODS:Two 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). RESULTS:Our 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; I2 = 93%) or recessive model (OR: 1.28; 95% CI: 0.89 to 1.84; p = 0.18; I2 = 82%) or dominant model (OR: 1.20; 95% CI: 0.92 to 1.56; p = 0.17; I2 = 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. CONCLUSION:K469E 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.

SUBMITTER: Nepal G

PROVIDER: S-EPMC6625125 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Nepal Gaurav G Yadav Jayant Kumar JK Kong YuHui Y

Molecular genetics & genomic medicine 20190603 7

<h4>Background</h4>The 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 ...[more]

PMID: 31157518

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Project description:Background: Although numerous epidemiological studies have investigated the association between -174G/C(rs1800795) polymorphism in the interleukin-6 (IL-6) gene-stimulatory region and the risk of ischemic stroke (IS), they failed to reach a unified conclusion. The true relationship between -174G/C(rs1800795) polymorphism and IS remains controversial and unclear. Therefore, in this meta-analysis, we aimed to analyze more precisely the association between -174G/C(rs1800795) single-nucleotide polymorphism (SNP) of IL-6 gene and IS in a larger pooled population. Methods: A comprehensive literature search was performed in PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials until June 30, 2021. A fixed or random-effects model was utilized based on heterogeneity between studies. The odds ratios (ORs) and 95% confidence intervals (Cis) were calculated in the models of allele comparison (G vs. C), homozygote comparison (GG vs. CC) and (GC vs. CC), dominant (GG vs. GC + CC), hyper dominant (GG + CC vs. GC), and recessive (GG + GC vs. CC) to determine the strength of associations. Results: This meta-analysis included 13 case-control studies in 35 articles with 5,548 individuals. Overall, no significant associations between IL-6 -174G/C(rs1800795) and IS were identified (G vs. C:OR [95% CI] = 0.99 [0.81, 1.21], P = 0.91; GG + CC vs. GC:0.97 [0.85, 1.11], P = 0.66; GG vs. GC + CC: 1.01 [0.81, 1.25], P = 0.94; GC vs. CC: OR [95% CI] = 1.01 [0.68, 1.5], P = 0.96; GG vs. CC:0.93 [0.57, 1.51], P = 0.76; GG + GC vs. CC:0.97 [0.64, 1.47], P = 0.89). In the subgroup analyses by ethnicity or HWE P-value, there was a statistically significant association between IL-6 -174G/C(rs1800795) polymorphisms and IS in the alleles model; (G vs. C: LogOR [95% CI] = 0.14 [-0.16,.45], P = 0.00), homozygote model (GG vs. CC: LogOR [95% CI] = 0.18 [-0.58,.95], P = 0.00) and (GC vs. CC: LogOR [95% CI] = 0.2 [-0.46,.85], P = 0.00), dominant model (GG vs. GC + CC: OR [95% CI] = 0.02 [-0.72, 0.77], P = 0.00), and recessive model (GG + GC vs. CC: OR [95% CI]= -0.17 [-0.86,.52], P = 0.00) of the European population and in the dominant model (GG vs. GC + CC: OR [95% CI] = -0.13 [-0.51, 0.24]) of the Asian population. No statistical significance was identified in both six models of HWE p ≥ 0.2 group (both P ≥ 0.05). Conclusion: This meta-analysis revealed no correlation between IL-6 -174G/C(rs1800795) polymorphism and IS, whereas the subgroup analysis indicated that the relationship between IL-6 -174G/C(rs1800795) polymorphism and IS susceptibility varied significantly according to ethnicity and geography.

Project description:BACKGROUND:Endothelin (ET)-1 is a potent vasoconstrictor peptide produced by endothelial cells and associated with vascular dysfunction and cardiovascular disease. Lys198Asn is a single-nucleotide polymorphism (SNP) of gene encoding ET-1 (EDN1). It is hypothesized that it might have a role in altering ET-1 and ultimately leading to vascular dysfunction and ischemic stroke. We therefore conducted a meta-analysis to investigate the association between Lys198Asn polymorphism of EDN1 gene and susceptibility of ischemic stroke. METHODS:This meta-analysis was conducted according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched PubMed, Google Scholar, Embase, Web of Science, J-STAGE, and China National Knowledge Infrastructure (CNKI) for relevant studies. The association between Lys198Asn polymorphism and ischemic stroke susceptibility was evaluated by calculating the pooled ORs and 95% CIs. RESULTS:Our analysis included 1,291 cases and 2,513 controls. Meta-analysis established a significant association between Lys198Asn SNP of EDN1 gene and ischemic stroke when assuming either recessive model (OR: 1.30; 95% CI: 1.02-1.65; p = .03; I2 = 41%) or dominant model (OR: 1.48; 95% CI: 1.24-1.76; p < .001; I2 = 61%). There was no evidence of publication bias in either of the recessive model (Egger test: p = .23; Begg test: p = .85) or dominant model (Egger test: p = .79; Begg test: p = .85). A subgroup analysis based on subtypes of ischemic stroke showed that Lys198Asn SNP was only associated with large vessel infarction but not with lacunar infarction caused by small vessel disease. A subgroup analysis based on ethnicity revealed that the Lys198Asn polymorphism of the EDN1 gene was associated with ischemic stroke only in Caucasians. CONCLUSIONS:The present meta-analysis suggests that Lys198Asn polymorphism of EDN1 gene is associated with an increased risk for ischemic stroke.

Dataset Information

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

Publications

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

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