VEGF Receptor-2 Variants Are Associated With Susceptibility to Stroke and Recurrence

Zhang, Weili; Sun, Kai; Zhen, Yang; Wang, Daowen; Wang, Yibo; Chen, Jinxing; Xu, Jianfeng; Hu, Frank B.; Hui, Rutai

doi:10.1161/strokeaha.109.554394

Cited by 40 publications

(67 citation statements)

References 26 publications

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“…Previous genotyping results reported by other researchers involving these two SNPs of the VEGFR2 gene had been controversial. Wang et al [33] reported that Han Chinese with the C allele for rs2071559 had a higher risk of coronary heart disease, while Zhang et al [16] reported that Han Chinese with the C allele had a lower risk in susceptibility to stroke and recurrence. In addition, a study on another Asian population involving Japanese subjects reported no significant associations between the two VEGFR2 gene SNPs, rs1870377 and rs2071559, on the development of coronary artery lesion with Kawasaki disease subjects [34].…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, no evidence has so far been reported that these two SNPs (rs1870377 and rs2071559) are in linkage disequilibrium, but a recent paper has described that the A-C-A-T-G haplotype of the VEGFR2 gene contained complete linkage between rs1870377 and rs6838752 (tag SNP) [15]. Zhang et al [16] have also reported a strong linkage disequilibrium among the three common variants found in the promoter region, rs2071559, rs9994560 and rs7667298.…”

Section: Introductionmentioning

confidence: 99%

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Interaction between <i>VEGF Receptor-2</i> Gene Polymorphisms and Dietary Patterns on Blood Glucose and Lipid Levels in Chinese Malaysian Adults

et al. 2011

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Background/Aims: The prevalence of lifestyle-related chronic diseases is increasing and gene-diet interaction studies are limited among the Malaysian population. This study was conducted to evaluate the association and interaction effects of vascular endothelial growth factor receptor-2(VEGFR2) gene polymorphisms and dietary patterns on anthropometric and biochemical risk factors of chronic diseases in 179 Chinese Malaysian adults. Methods: Genotyping of rs1870377 and rs2071559 was performed by real-time PCR using TaqMan probes. Dietary patterns were constructed from the food frequency questionnaire using factor analysis. Anthropometric measurements: body mass index (BMI), systolic and diastolic blood pressure and biomarkers: blood glucose, glycated hemoglobin A1c (HbA1c) and lipids were obtained. Results: Two dietary patterns: ‘Balanced diet’ and ‘Meat, rice and noodles diet’ (MRND) were extracted. MRND was associated with higher BMI, blood pressure, blood glucose and lipids, while T alleles in both rs1870377 and rs2071559 were associated with higher blood lipids (p < 0.05). The interaction of MRND and rs1870377 had a borderline effect on blood HbA1c after adjusting for confounders (p = 0.057). Conclusions: A dietary pattern of MRND and VEGFR2 gene polymorphisms were both associated with increased health risks of lifestyle-related chronic diseases particularly blood glucose and lipid levels in Chinese Malaysian adults.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interaction between <i>VEGF Receptor-2</i> Gene Polymorphisms and Dietary Patterns on Blood Glucose and Lipid Levels in Chinese Malaysian Adults

et al. 2011

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“…22 The criteria of diagnosis and recruitment were given in details in Supplemental Materials (http://stroke.ahajournals.org). Before data assessment, we excluded 679 subjects because of lack of definite diagnosis (24 cases), absence of plasma (76 cases, 93 control subjects), and insufficient DNA (243 cases, 243 control subjects).…”

Section: Stroke Sample Populationmentioning

confidence: 99%

Variants on Chromosome 9p21.3 Correlated With ANRIL Expression Contribute to Stroke Risk and Recurrence in a Large Prospective Stroke Population

Zhang

Chen²,

Liu³

et al. 2012

Stroke

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Background and Purpose-ANRIL encodes a long antisense noncoding RNA in the INK4 locus. Although ANRIL has been proven to be associated with coronary heart disease, its roles in stroke are inconsistent, and sparse data are available regarding hemorrhagic stroke. Methods-A Chinese case-control study was conducted, comprising 1657 cases (724 atherothrombosis, 466 lacunar infarction, and 462 hemorrhagic strokes) and 1664 controls. Stroke patients were prospectively followed-up for a median of 4.5 (range, 0.1-6.0) years. Expression of ANRIL transcripts was examined in 42 human atherosclerotic plaques. Results-After adjustment for vascular risk factors and correction for multiple comparisons, subjects carrying the GG genotype of rs10757278 had 1.47-fold (95% CI, 1.11-1.89; Pϭ0.05) and 1.60-fold (95% CI, 1.16 -2.15; Pϭ0.04) increased risk for atherothrombotic and hemorrhagic strokes, respectively. During the follow-up, 317 recurrent strokes and 301 deaths from all causes were documented. Subjects carrying rs10757278GG had higher risk for stroke recurrence (relative risk [RR],1.56; 95% CI,1.15-2.12; Pϭ0.005) and cardiovascular mortality (RR, 2.0; 95% CI, 1.26 -3.18; Pϭ0.003), respectively. Rs10757274 was also associated with stroke risk and recurrence. Family history of stroke further increased the stroke risk by 2.37-fold (95% CI, 1.38 -4.06; Pϭ0.01) and recurrent stroke risk by 2.45-fold (95% CI, 1.56 -3.86; PϽ0.0001) respectively, when compared with those carrying none of G-alleles and without family history. Finally, rs10757278 was associated with differential expression of the ANRIL transcripts. Conclusions-Our findings indicated that the ANRIL may serve as a novel genetic marker for the risk of atherothrombotic and hemorrhagic stroke and their recurrence. (Stroke. 2012;43:14-21.)Key Words: chromosome 9p21.3 Ⅲ follow-up studies Ⅲ genetics Ⅲ risk factors S troke is a major cause of death and disability worldwide and in China. Survivors are often disabled, require long-term care, and are at high risk of recurrence. Among subtypes of stroke, hemorrhagic stroke accounts for 20% to 40% in the Chinese population; in contrast, the majority (80 -90%) of strokes are cerebral infarctions in most western populations. 1 The reasons for high risk of stroke, especially hemorrhagic stroke, among the Chinese, remain unknown. The contribution of genetic risk to stroke is still not completely understood.It is generally accepted that genetic variants on chromosome 9p21.3 are associated with the risk of coronary artery disease, 2-4 but its roles in stroke are inconsistent. [5][6][7][8][9][10][11][12] A recent meta-analysis 13 showed that the association of 9p21.3 with stroke is only confined to the subtype of large-vessel strokes. However, a recent genome-wide association study showed that the 9p21.3 region is also implicated in risk for intracranial aneurysm, in which atherosclerosis is not thought to play a major role. 14 Therefore, additional studies are needed to determine the mechanisms by which the 9p21.3 region affects vascular...

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“…26 -32 Recently, Yang et al 33 reported therapeutic effects of different doses of intranasal VEGF on angiogenesis and functional recovery of ischemic brains in adult rats. The VEGF -1154GϾA (rs1570360) and -634GϾC (rs2010963) polymorphisms in patients with ischemic stroke alone have been studied in the Chinese population, 34 although no significant findings were demonstrated. However, to our knowledge, the effects of the VEGF -2578CϾA (rs699947) and 936CϾT (rs3025039) polymorphisms on the risk of stroke and SBI have not been evaluated previously.…”

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confidence: 99%

Association Between VEGF Polymorphisms and Homocysteine Levels in Patients With Ischemic Stroke and Silent Brain Infarction

Hong

Kim

et al. 2011

Stroke

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Background and Purpose-Vascular endothelial growth factor (VEGF) plays a role in atherosclerosis-related diseases such as cerebrovascular or cardiovascular diseases. However, the effect of VEGF -2578CϾA, -1154GϾA, -634GϾC, and 936CϾT polymorphisms on the susceptibility to stroke and silent brain infarction has not been reported. Methods-Using polymerase chain reaction-amplified DNA, VEGF polymorphisms were analyzed in 615 patients with ischemic stroke, 376 patients with silent brain infarction, and 494 control subjects. Results-The AA and CCϩCA (C allele bearing) genotype frequencies of the -2578CϾA polymorphism and the CTϩTT (T allele-bearing) genotype frequency of the 936CϾT polymorphism were significantly different between the stroke and control groups (false discovery rate-adjusted probability values of 0.016, 0.044, and 0.044, respectively). When stratified by the size of the occluded vessel, the VEGF polymorphisms were associated with patients with multiple small-artery occlusions. Several haplotypes of the VEGF polymorphisms were significantly different between the control and stroke groups. With respect to silent brain infarction, the difference in the frequency of the -634GϾC polymorphism between the GCϩCC (C allele-bearing) genotype and the controls was marginally significant (false discovery rate-adjusted probability value of 0.056). On the other hand, the -634GϾC and 936CϾT polymorphisms were associated with plasma homocysteine levels of patients with multiple or single small-artery occlusions, respectively. Conclusions-This study suggests that VEGF polymorphisms and haplotypes are possible genetic determinants for the risk of ischemic stroke, particularly in patients with multiple small-artery occlusions. However, VEGF polymorphisms had only a weak association with plasma homocysteine levels in the Korean population. (Stroke. 2011;42:2393-2402.)

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VEGF Receptor-2 Variants Are Associated With Susceptibility to Stroke and Recurrence

Cited by 40 publications

References 26 publications

Interaction between <i>VEGF Receptor-2</i> Gene Polymorphisms and Dietary Patterns on Blood Glucose and Lipid Levels in Chinese Malaysian Adults

Interaction between <i>VEGF Receptor-2</i> Gene Polymorphisms and Dietary Patterns on Blood Glucose and Lipid Levels in Chinese Malaysian Adults

Variants on Chromosome 9p21.3 Correlated With ANRIL Expression Contribute to Stroke Risk and Recurrence in a Large Prospective Stroke Population

Association Between VEGF Polymorphisms and Homocysteine Levels in Patients With Ischemic Stroke and Silent Brain Infarction

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