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A genetic study of the NOS3 gene for ischemic stroke in a Chinese population.

ABSTRACT: We recruited 560 unrelated patients with ischemic stroke and 153 unrelated controls to undertake a genetic analysis for association between the NOS3 gene and ischemic stroke. All the subjects were Chinese of Han descent. Because the NOS3 gene spans about 21 kb of DNA and contains 26 exons, we selected a single nucleotide polymorphism (SNP) rs3918181, an A to G base change located in intron 14 of the gene, as a DNA marker. PCR-based restriction fragment length polymorphism analysis was applied to genotype rs3918181 (RsaI site). The chi-square (chi(2)) goodness-of-fit test showed that the genotypic distributions of the marker were not deviated from Hardy-Weinberg equilibrium in both the patient group (chi(2) = 0.166, p = 0.684) and the control group (chi(2) = 0.421, p = 0.517). The cocaphase analysis showed allelic association of rs3918181 with ischemic stroke in males (chi(2) = 4.04, p = 0.044, OR = 1.43, 95% CI 1.01 approximately 2.02) and frequency of allele A was significantly higher in male patients than male control subjects. The chi(2) test revealed genotypic association between rs3918181 and ischemic stroke in males (chi(2) = 4.26, df = 1, p = 0.039, OR = 1.61, 95% CI 1.02 approximately 2.53) but not in females. The present work suggests that rs3918181 is associated with ischemic stroke in male patients. This finding gives further evidence in support of the eNOS association with ischemic stroke in the Chinese population.

SUBMITTER: Du D

PROVIDER: S-EPMC2840541 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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A genetic study of the NOS3 gene for ischemic stroke in a Chinese population.

Du Danhua D Gao Peng P Hu Linsen L Yang Yumei Y Wang Feng F Ye Lin L Zhang Xuan X Chang Ming M Zhao Jiexu J Wu Jiang J Megson Ian L IL Wei Jun J

International journal of general medicine 20081130

We recruited 560 unrelated patients with ischemic stroke and 153 unrelated controls to undertake a genetic analysis for association between the NOS3 gene and ischemic stroke. All the subjects were Chinese of Han descent. Because the NOS3 gene spans about 21 kb of DNA and contains 26 exons, we selected a single nucleotide polymorphism (SNP) rs3918181, an A to G base change located in intron 14 of the gene, as a DNA marker. PCR-based restriction fragment length polymorphism analysis was applied to ...[more]

PMID: 20428408

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Project description:Background and purposeIschemic 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.Materials and methodsIn 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.ResultsWe 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).ConclusionThe 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

A genetic study of the NOS3 gene for ischemic stroke in a Chinese population.

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A genetic study of the NOS3 gene for ischemic stroke in a Chinese population.

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