Association between kinase insert domain-containing receptor gene polymorphisms and silent brain infarction: A Korean study

Han, Inbo; Kim, Ok-Su; Ropper, Alexander E.; Cho, Yun-Kyung; Teng, Yang D.

doi:10.1016/j.jns.2012.03.020

Cited by 10 publications

(6 citation statements)

References 32 publications

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“…Similarly, vascular degeneration and formation of weak, thin-walled vasculature can reduce vessel compliance and increase the risk of spontaneous vessel wall rupture and ICH under some stresses such as hypertension and increased shear stress 34 , 40 . In contrast, the allele -604G could exert a protective effect on large-artery atherosclerosis by reducing neovascularisation and inflammation, retarding atherosclerotic lesions growth and the plaque destabilization leading to rupture in major cranial arteries 34 , 35 . Albeit the decrease in VEGFR2 function could inhibit atherosclerosis, a damaging effect diminishing the maintenance of endothelial integrity may be more profound 35 .…”

Section: Discussionmentioning

confidence: 98%

“…In another Chinese study, the + 1192A allele was associated not only with increased susceptibility to intracerebral haemorrhage (ICH), but also it was a prognostic factor for stroke recurrence, whereas the -604G allele predicted a reduced susceptibility to atherothrombotic stroke and stroke recurrence, and was reversely correlated with carotid artery intima media thickness 34 . Thereafter, Han et al described a higher risk of silent brain infarcts in men and younger than 65 years carrying the -604G allele in a Korean population 35 .…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the different consequences for different strokes subtypes of genetic variants in VEGFR2 gene could be explained by a dual role of the VEGF-VEGFR2 system, enhancing both physiological and pathological angiogenesis 35 . It has been proposed that the allele -604G in VEGFR2 gene, by down-regulating VEGF-VEGFR2 signalling, causes disrupted endothelial cell development and defective blood vessel formation, decreases the integrity of vascular endothelium as well as inhibits endothelial repair, eventually leading to small-arterial occlusion and SVD 34 , 35 , 39 . Similarly, vascular degeneration and formation of weak, thin-walled vasculature can reduce vessel compliance and increase the risk of spontaneous vessel wall rupture and ICH under some stresses such as hypertension and increased shear stress 34 , 40 .…”

Section: Discussionmentioning

confidence: 99%

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Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease

Manso-Calderón,

Cacabelos-Pérez,

Sevillano-García

et al. 2023

Sci Rep

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There is increasing evidence for the involvement of blood–brain barrier (BBB) in vascular dementia (VaD) and Alzheimer´s disease (AD) pathogenesis. However, the role of endothelial function-related genes in these disorders remains unclear. We evaluated the association of four single-nucleotide polymorphisms (VEGF, VEGFR2 and NOS3) with diagnosis and rate of cognitive decline in AD and VaD in a Spanish case–control cohort (150 VaD, 147 AD and 150 controls). Participants carrying -604AA genotype in VEGFR2 (rs2071559) were less susceptible to VaD after multiple testing. Further analysis for VaD subtype revealed a significant difference between small-vessel VaD patients and controls, but not for large-vessel VaD patients. In addition, -2578A and -460C alleles in VEGF (rs699947 and rs833061) showed to decrease the risk of AD, whereas NOS3 (rs1799983) influenced disease progression. Our study supports previous findings of a deleterious effect of VEGFR2 reduced expression on small-vessel disease, but not on large-vessel disease; as well as a detrimental effect of down-regulating VEGF and eNOS in AD, affecting vascular permeability and neuronal survival. These data highlight the relevance of endothelial function and, therefore, BBB in both VaD and AD.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease

Manso-Calderón,

Cacabelos-Pérez,

Sevillano-García

et al. 2023

Sci Rep

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“…The clinical and pathological aspects of SBI are distinct from those of ischemic stroke; while vascular brain lesions are evident using magnetic resonance imaging (MRI), SBI is clinically asymptomatic (1,2). SBI and white matter lesions are frequently observed using brain MRI in healthy elderly individuals and are associated with an increased risk of stroke and dementia (1)(2)(3)(4)(5)(6).…”

Section: Silent Brain Infarction (Sbi) Is a Cerebrovascular Disordermentioning

confidence: 99%

“…SBI and white matter lesions are frequently observed using brain MRI in healthy elderly individuals and are associated with an increased risk of stroke and dementia (1)(2)(3)(4)(5)(6). SBI is a risk factor for stroke (7).…”

Section: Silent Brain Infarction (Sbi) Is a Cerebrovascular Disordermentioning

confidence: 99%

Association between common genetic variants of α2A-, α2B- and α2C-adrenoceptors and the risk of silent brain infarction

Kim

Jeon

Kim

et al. 2014

Molecular Medicine Reports

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Abstract. Silent brain infarction (SBI) is an asymptomatic cerebrovascular disorder. The aim of the present study was to investigate the association between adrenoceptor-α2 (ADRA2) gene polymorphisms and SBI. A total of 361 patients with SBI and 467 healthy control subjects were examined. The polymerase chain reaction was performed to genotype the ADRA2A 1780G>A, ADRA2B 301-303 insertion/deletion (I/D) and ADRA2C 322-325I/D polymorphisms. The frequency of the ADRA2C 322-325I/D polymorphism was significantly different between patients with SBI and control subjects. When interaction analyses were performed for vascular risk factors, the ADRA2C 322-325ID genotype increased the risk for SBI in the presence of hypertension and elevated plasma homocysteine levels. The ADRA2C 322-325ID genotype and plasma homocysteine levels showed a significant synergistic effect for SBI. In addition, the ADRA2A 1780AA genotype was associated with elevated plasma homocysteine levels. Although further analysis of the association between ADRA2 polymorphisms and clinical risk factors of SBI is required, the present study of a limited set of SBI risk factors with ADRA2 polymorphisms provides the first evidence of the involvement of ADRA2 gene family members in the development of SBI. Further studies using larger and more heterogeneous populations are required to validate the association of ADRA2 polymorphisms with SBI. Introduction Silent brain infarction (SBI) is a cerebrovascular disorder.The clinical and pathological aspects of SBI are distinct from those of ischemic stroke; while vascular brain lesions are evident using magnetic resonance imaging (MRI), SBI is clinically asymptomatic (1,2). SBI and white matter lesions are frequently observed using brain MRI in healthy elderly individuals and are associated with an increased risk of stroke and dementia (1-6). SBI is a risk factor for stroke (7). SBI has been associated with several cardiovascular risk factors. Previous studies strongly suggest that SBI can be significantly influenced by multiple risk factors, including hypertension, homocysteine levels, cigarette smoking and metabolic syndrome (7-11). However, relatively little is known about the genes involved in SBI pathogenesis. The present study was a candidate gene association study focusing on the association between the adrenoceptor-α2 (ADRA2) genes and SBI. The rationale was two-fold: i) ADRA2 genes are responsible for blood flow vasoconstriction, which is linked to thrombosis; ii) ADRA2 defects are associated with an increased likelihood of ischemic stroke (12,13).There are three subtypes of α2-adrenoceptors (α2-ARs), α2A, α2B and α2C, which are encoded by the ADRA2A, ADRA2B and ADRA2C genes, respectively (10,11). The α2-AR, a membrane receptor for norepinephrine and epinephrine, mediates physiological responses to endogenous catecholamine. The α2-AR is involved in blood pressure reduction, inhibition of presynaptic neurotransmitter release, lipolysis and insulin secretion, as well as augmentation of platelet aggregation (13)...

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A meta‐analysis of the relationship between VEGFR2 polymorphisms and atherosclerotic cardiovascular diseases

Wang

Peng

et al. 2019

Clinical Cardiology

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Background Some previous studies explored associations between vascular endothelial growth factor receptor 2 (VEGFR2) polymorphisms and atherosclerotic cardiovascular diseases (ASCVD), with conflicting findings. Hypothesis We thought that VEGFR2 polymorphisms may influence susceptibility to ASCVD. Here, we aimed to better analyze the relationship between VEGFR2 polymorphisms and ASCVD in a larger combined population by performing a meta‐analysis. Methods We searched Pubmed, Embase, and Web of Science for related articles. We calculated odds ratio (OR) and 95% confidence interval (CI) to estimate whether there are genetic associations between VEGFR2 polymorphisms and ASCVD. Results Ten studies were included for this meta‐analysis (5474 cases and 8584 controls). VEGFR2 rs1870377 (dominant comparison: 0.81 (0.73‐0.89), I2 = 56%; recessive comparison: 1.40 (1.25‐1.57), I2 = 34%; allele comparison: 0.81 (0.76‐0.87), I2 = 0%), rs2071559 (dominant comparison: 0.83 (0.76‐0.91), I2 = 0%; recessive comparison: 1.22 (1.07‐1.38), I2 = 0%; allele comparison: 0.86 (0.81‐0.92), I2 = 0%) and rs2305948 (dominant comparison: 0.79 (0.72‐0.87), I2 = 25%; recessive comparison: 1.44 (1.08‐1.92), I2 = 60%; allele comparison: 0.79 (0.68‐0.92), I2 = 73%) polymorphisms were all found to be significantly associated with susceptibility to ASCVD in general population. Subgroup analyses by type of disease revealed similar significant findings for rs1870377, rs2071559, and rs2305948 polymorphisms in coronary artery disease (CAD) subgroup. Besides, positive results were also found for rs1870377 polymorphism in ischemic stroke (IS) subgroup. Conclusions In summary, this meta‐analysis proved that these VEGFR2 polymorphisms could be used to identify individual with elevated susceptibility to ASCVD.

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Association between kinase insert domain-containing receptor gene polymorphisms and silent brain infarction: A Korean study

Cited by 10 publications

References 32 publications

Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease

Analysis of endothelial gene polymorphisms in Spanish patients with vascular dementia and Alzheimer´s disease

Association between common genetic variants of α2A-, α2B- and α2C-adrenoceptors and the risk of silent brain infarction

A meta‐analysis of the relationship between VEGFR2 polymorphisms and atherosclerotic cardiovascular diseases

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