Dataset Information

Association of Apolipoprotein C3 Genetic Polymorphisms with the Risk of Ischemic Stroke in the Northern Chinese Han Population.

ABSTRACT: The apolipoprotein C3 (APOC3) gene, which is a member of the APOA1/C3/A4/A5 gene cluster, plays a crucial role in lipid metabolism. Dyslipidemia is an important risk factor for ischemic stroke. In the present study, we performed a hospital-based case-control study of 895 ischemic stroke patients and 883 control subjects to examine the effects of four APOC3 single nucleotide polymorphisms (SNPs) (rs2854116, rs2854117, rs4520 and rs5128) on the risk of ischemic stroke in a northern Chinese Han population. The SNaPshot Multiplex sequencing assay was used for SNP genotyping, and the potential association of genotype distributions and allele frequencies with ischemic stroke was analyzed statistically. Compared with the GG genotype, the CC+GC genotype of rs5128 was significantly associated with an increased risk in females (adjusted OR = 3.38, 95% CI = 1.82-6.28, P <0.01) after all of the risk factors were adjusted for with logistic regression analyses. A similar relationship was found between the rs4520 polymorphism and ischemic stroke risk in Han Chinese women. Under a recessive genetic model, the TT+TC genotypes of this variant increased ischemic stroke risk (adjusted OR = 2.05; 95% CI = 1.28-3.29; P <0.01). Haplotype analysis revealed that in males, the T-C-T-C haplotype of rs2854116-rs2854117-rs4520-rs5128 was significantly more frequent in the ischemic stroke group than in the control group (OR = 1.49, 95% CI = 1.18-1.87, P<0.01). The results of our study indicate that the APOC3 polymorphisms contribute to ischemic stroke susceptibility in females in the northern Chinese Han population.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5045204 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Association of Apolipoprotein C3 Genetic Polymorphisms with the Risk of Ischemic Stroke in the Northern Chinese Han Population.

Wang Yanzhe Y Yin Xiaoyu X Li Lei L Deng Shumin S He Zhiyi Z

PloS one 20160930 9

The apolipoprotein C3 (APOC3) gene, which is a member of the APOA1/C3/A4/A5 gene cluster, plays a crucial role in lipid metabolism. Dyslipidemia is an important risk factor for ischemic stroke. In the present study, we performed a hospital-based case-control study of 895 ischemic stroke patients and 883 control subjects to examine the effects of four APOC3 single nucleotide polymorphisms (SNPs) (rs2854116, rs2854117, rs4520 and rs5128) on the risk of ischemic stroke in a northern Chinese Han pop ...[more]

PMID: 27690381

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Project description:BackgroundApolipoprotein E (apoE) induces the uptake of vitamin K-rich lipoproteins by the liver, which likely affects inter-individual variation of warfarin dosing requirements. Associations between APOE polymorphisms and warfarin dosing were previously reported inconsistently among different ethnic groups, so the present study investigated this association in northern Han Chinese patients with mechanical heart valve prosthesis.MethodsA total of 186 patients who underwent mechanical heart valve replacement and attained a stable warfarin dose were included. APOE single nucleotide polymorphisms (SNPs) rs7412 and rs429358 were genotyped using Illumina SNP GoldenGate Assay. Genotyping results were confirmed by direct sequencing. PHASE v2.1 software was used to construct rs7412 and rs429358 haplotypes. The effects of different APOE genotypes on warfarin dose were analyzed statistically.ResultsThe mean warfarin maintenance dose was 3.10 ± 0.96 mg/day, and the mean international normalized ratio (INR) was 2.09 ± 0.24. APOE E2, E3, and E4 allele frequencies were 11.6 %, 82.5 %, and 5.9 %, respectively. No E2/E2 or E4/E4 genotypes were detected in this population. E2/E3, E3/E3, E2/E4, and E3/E4 genotype frequencies were 21.0 %, 67.2 %, 2.2 %, and 9.7 %, respectively. Significant differences in warfarin dose requirements were observed among patients with E2/E3, E3/E3, and E3/E4 genotypes (p < 0.05). In post hoc comparison, daily warfarin maintenance doses were significantly higher in E2/E3 heterozygotes compared with E3/E3 homozygotes (p < 0.05), but no differences in dose requirements were found between E3/E4 and E3/E3, or E2/E3 and E3/E4 (p > 0.05). Patients were divided into low-intensity anticoagulant treatment group (1.6 ≤ INR <2.0) and relatively high-intensity anticoagulant treatment group (2.0 ≤ INR ≤ 2.5), and significantly higher warfarin dose requirements were observed in E2/E3 heterozygotes compared with E3/E3 homozygotes in both subgroups (p < 0.05). Multivariable analysis adjusting for other confounders showed that E2/E3 genotype was associated with a significantly higher warfarin dose compared with E3/E3 genotype (p < 0.05).ConclusionsAPOE allele and genotype frequencies in the northern Han Chinese population appear to differ from other racial groups or populations living in other regions of China. The APOE E2 variant was associated with a significantly higher warfarin maintenance dose. Thus, APOE polymorphisms could be one of the predictors influencing warfarin doses in this population.

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.

Project description:Two common polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012 (approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group (P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke (OR = 1.844, 95% CI: 1.286-2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke (OR = 1.366, 95% CI: 1.077-1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype (OR = 2.953, 95% CI: 2.082-4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction (OR = 3.404, 95% CI: 1.631-7.102, P < 0.001) and additive interaction (RERI = 41.705, 95% CI: 14.586-68.824, AP = 0.860; 95% CI: 0.779-0.940; S = 8.170, 95% CI: 3.772-17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele (OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele (OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.

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.

Dataset Information

Association of Apolipoprotein C3 Genetic Polymorphisms with the Risk of Ischemic Stroke in the Northern Chinese Han Population.

Publications

Association of Apolipoprotein C3 Genetic Polymorphisms with the Risk of Ischemic Stroke in the Northern Chinese Han Population.

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