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Lack of association between ALOX5AP genetic polymorphisms and risk of ischemic stroke: evidence from meta-analyses.

ABSTRACT: Background:In recent years, there has been substantial research evaluating the relationship between arachidonate 5-lipoxygenase-activating protein (ALOX5AP) polymorphisms and ischemic stroke (IS). The objective of this study was to systematically review and analyze the existing evidence. Methods:A comprehensive search of major electronic databases for studies published between 1990 and 2018 was carried out. Data were synthesized as OR and 95% CI using fixed-effects and random-effects models. Results:A total of 30 studies were available for analysis. The aggregate sample size across all studies was 32,782 (16,294 cases and 16,488 controls). We found no association of the ALOX5AP rs10507391 (OR=1.03 for A allele vs T allele; 95% CI: 0.93-1.14; P=0.557), rs4769874 (OR=1.13 for A allele vs G allele; 95% CI: 1.00-1.28; P=0.050), rs9551963 (OR=1.03 for A allele vs C allele; 95% CI: 0.96-1.11; P=0.372), rs17222814 (OR=1.09 for A allele vs G allele; 95% CI: 0.96-1.24; P=0.195), rs17222919 (OR=0.89 for G allele vs T allele; 95% CI: 0.75-1.06; P=0.175), and rs4073259 (OR=1.20 for A allele vs G allele; 95% CI: 1.00-1.45; P=0.056) polymorphisms with IS risk. Haplotype analysis also did not yield significant findings for the HapA (rs17222814G-rs10507391T-rs4769874G-rs9551963A; OR=1.20; 95% CI: 0.91-1.56; P=0.192) and HapB (rs17216473A-rs10507391A-rs9315050A-rs17222842G; OR=1.11; 95% CI: 0.90-1.38; P=0.339) haplotypes. Conclusion:Current evidence does not support an association of rs10507391, rs4769874, rs9551963, rs17222814, rs17222919, rs4073259, and HapA and HapB with IS risk.

SUBMITTER: Zheng JH

PROVIDER: S-EPMC6354695 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Lack of association between <i>ALOX5AP</i> genetic polymorphisms and risk of ischemic stroke: evidence from meta-analyses.

Zheng Jing-Hui JH Ning Gui-Lan GL Xu Wen-Hua WH Wu Xin-Cheng XC Ma Xiao-Cong XC

Neuropsychiatric disease and treatment 20190125

<h4>Background</h4>In recent years, there has been substantial research evaluating the relationship between arachidonate 5-lipoxygenase-activating protein (<i>ALOX5AP</i>) polymorphisms and ischemic stroke (IS). The objective of this study was to systematically review and analyze the existing evidence.<h4>Methods</h4>A comprehensive search of major electronic databases for studies published between 1990 and 2018 was carried out. Data were synthesized as OR and 95% CI using fixed-effects and rand ...[more]

PMID: 30774347

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Project description:BackgroundPolymorphisms in the CYP1A2 genes have the potential to affect the individual capacity to convert pre-carcinogens into carcinogens. With these comprehensive meta-analyses, we aimed to provide a quantitative assessment of the association between the published genetic association studies on CYP1A2 single nucleotide polymorphisms (SNPs) and the risk of cancer.MethodsWe searched MEDLINE, ISI Web of Science and SCOPUS bibliographic online databases and databases of genome-wide association studies (GWAS). After data extraction, we calculated Odds Ratios (ORs) and 95% confidence intervals (CIs) for the association between the retrieved CYP1A2 SNPs and cancer. Random effect model was used to calculate the pooled ORs. Begg and Egger tests, one-way sensitivity analysis were performed, when appropriate. We conducted stratified analyses by study design, sample size, ethnicity and tumour site.ResultsSeventy case-control studies and one GWA study detailing on six different SNPs were included. Among the 71 included studies, 42 were population-based case-control studies, 28 hospital-based case-control studies and one genome-wide association study, including total of 47,413 cancer cases and 58,546 controls. The meta-analysis of 62 studies on rs762551, reported an OR of 1.03 (95% CI, 0.96-1.12) for overall cancer (P for heterogeneity < 0.01; I(2) = 50.4%). When stratifying for tumour site, an OR of 0.84 (95% CI, 0.70-1.01; P for heterogeneity = 0.23, I(2) = 28.5%) was reported for bladder cancer for those homozygous mutant of rs762551. An OR of 0.79 (95% CI, 0.65-0.95; P for heterogeneity = 0.09, I(2) = 58.1%) was obtained for the bladder cancer from the hospital-based studies and on Caucasians.ConclusionsThis large meta-analysis suggests no significant effect of the investigated CYP1A2 SNPs on cancer overall risk under various genetic models. However, when stratifying according to the tumour site, our results showed a borderline not significant OR of 0.84 (95% CI, 0.70-1.01) for bladder cancer for those homozygous mutant of rs762551. Due to the limitations of our meta-analyses, the results should be interpreted with attention and need to be further confirmed by high-quality studies, for all the potential CYP1A2 SNPs.

Project description:Ischemic stroke (IS) is the main cause of mortality and disability among the old people in China and is a multifactorial disease influenced by many factors including genetic factors like the allele for CYP 2J2. It has been demonstrated that CYP2J2 polymorphisms alter the transcriptional activity. However, studies on the association between CYP2J2-50G/T polymorphism and IS have reported conflicting results. Thus, our study aimed to examine the association between 4 variants in the CYP2J2 gene and the risk of IS and its subtypes, in the Chinese population.In this study, genotyping was performed by using polymerase chain reaction (PCR) sequencing for 202 IS patients and 206 age- and sex-matched controls. Odds ratios (ORs) and confidence interval (CI) were estimated by multivariate logistic regression and PCR results were confirmed by DNA sequencing. A meta-analysis was conducted to evaluate the association of CYP2J2-50G>T polymorphism with the risk of IS in Chinese population by calculating pooled OR.We found this polymorphism was significantly associated with IS (17.82% vs. 10.68%, P = 0.039). Multiple logistic regression analysis revealed that GT genotype was associated with a significantly high risk of IS (OR = 2.32, 95% CI: 1.21-4.45, P = 0. 011) after adjustment for other confounding factors such as hypertension, diabetes, heart disease, smoking habit, family history, triglyceride and low-density lipoprotein levels. We also found a significant association of GT genotype with small artery occlusion (SAA) (P < 0.05; OR = 2.22; 95% CI: 1.043-4.72). Meta-analysis results also showed that the GT genotype carriers had a negative effect on the risk of IS in Chinese population with overall OR of 1.40 (95% CI: 1.06-1.84).The findings of the present study suggested that polymorphism in -50G/T position of CYP2J2 gene might be a risk factor for IS in Chinese population. Further large prospective studies were required to confirm these findings.

Project description:Numerous genetic polymorphisms and clinical laboratory parameters are associated with ischemic stroke (IS). However, the results of such studies have frequently been inconsistent. The aim of the present study was to evaluate associations between clinical laboratory parameters with genetic polymorphisms that influence the risk of IS in a Chinese Han population. Clinical laboratory parameters were measured by an automatic biochemical analyzer. Genotype and allele frequencies of the polymorphisms angiotensin-converting enzyme (ACE) D/I, methylene tetrahydrofolate reductase (MTHFR) C677T and β-fibrinogen (β-Fg) A/G, 455/148T/C were characterized by restriction fragment length polymorphism-PCR. Furthermore, the gene polymorphisms plasminogen activator inhibitor (PAI)-1-4G/5G and apolipoprotein E (ApoE) ε2,3,4 were characterized by allele-specific PCR. The associations of genotype and allele frequencies of the six risk genes in different groups with clinical laboratory parameters were analyzed by chi-square tests. The distribution maps of the polymorphisms of the six genes and clinical laboratory parameters were compared between a control group of 336 healthy individuals and 762 patients with IS. Certain laboratory parameters were associated with ACE I/D, β-Fg-455 A/G and PAI-1 4G/5G. The D allele of ACE I/D was associated with high levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C). Furthermore, high levels of fasting blood glucose, triglyceride and LDL-C were risk factors for IS. There were significant differences in the genotype frequencies of ACE I/D, β-Fg-455 A/G and β-Fg-148 T/C between the IS and the control group. In conclusion, clinical laboratory parameters were associated with the risk of polymorphisms of IS-related genes. The present results support the determination of a range of control values of clinical laboratory parameters for common genotypes in patients with diabetes and hyperlipidemia as a strategy for the early prevention of IS.

Dataset Information

Lack of association between ALOX5AP genetic polymorphisms and risk of ischemic stroke: evidence from meta-analyses.

Publications

Lack of association between <i>ALOX5AP</i> genetic polymorphisms and risk of ischemic stroke: evidence from meta-analyses.

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