Ischemic stroke as a complex polygenic disease

Титов, Б. В.; Матвеева, Н. А.; Martynov, M. Yu.; Фаворова, О. О.

doi:10.1134/s0026893315020120

Cited by 19 publications

(8 citation statements)

References 165 publications

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“…As the major type of stroke, IS refers to cerebral necrosis caused by stenosis or occlusion of the cerebral artery, and cerebral insufficiency, which is a complex neurological disease induced by interaction of genes with the environment that causes permanently disabling disease [ 6 , 25 – 26 ]. One in six people in the world suffer from stroke [ 27 ], and IS seriously increases the burden on economy and medical resource in the world [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, these risk factors can only explain a small part of the etiology. IS is a complex disease induced by the combined action of a variety of genetic and environmental factors, and genetic mutations play a crucial role in its development [ 6 – 8 ]. Nevertheless, the exact molecular mechanism underlying the development of IS has not yet been determined.…”

Section: Introductionmentioning

confidence: 99%

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Association of miR-146a, miR-149, miR-196a2, miR-499 gene polymorphisms with ischemic stroke in a Chinese people

Luo

Wang

et al. 2017

Oncotarget

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This study aimed to investigate genetic polymorphisms of miR-146a, miR-149, miR-196a2, and miR-499 and genetic susceptibility of ischemic stroke in the population of Guangxi in China. A case–control study was used to investigate miRNAs genetic polymorphisms in 298 patients with ischemic stroke and 303 healthy controls. Single-base extension polymerase chain reaction genotyping principle was used to detect genetic polymorphisms of miRNAs,and the relationship of genotype in each group and blood lipid was compared and analyzed. The genetic polymorphism of miR-499A>G (rs3746444) was associated with ischemic stroke (P < 0.05), and the risk of ischemic stroke was high in patients with G allele (OR = 1.455; 95% CI = 0.531–2.381; P = 0.039) and AG (OR = 1.339; 95% CI = 1.126–1.967; P = 0.037) genotype. The levels of low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, homocysteine, and lipoprotein in the ischemic stroke group were higher than those in the control group (P < 0.05). The genetic polymorphism of miR-499A>G (rs3746444) was related to ischemic stroke, and G allele and AG genotype may increase the risk of ischemic stroke in the population of Guangxi in China.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of miR-146a, miR-149, miR-196a2, miR-499 gene polymorphisms with ischemic stroke in a Chinese people

Luo

Wang

et al. 2017

Oncotarget

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“…Thus, recent studies suggest ERK5/KLF4 cascade as a common downstream signaling pathway for NGF-induced neuroprotection against oxidative stress [ 11 ]. Hence NGF is involved in several crucial processes related to IS etiopathogenesis and it is a good candidate to influence the susceptibility to IS, which is considered to be a complex polygenic disease [ 12 ]. There are number of single nucleotide polymorphisms (SNPs) in genes encoding NGF and NGFR that may alter their function and expression levels [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Involvement of polymorphisms of the nerve growth factor and its receptor encoding genes in the etiopathogenesis of ischemic stroke

Stepanyan

Zakharyan

Simonyan³

et al. 2018

BMC Med Genet

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BackgroundDespite the important role of the nerve growth factor in the survival and maintenance of neurons in ischemic stroke, data regarding the relationships between variations in the encoding gene and stroke are lacking. In the present study, we evaluated the association of the functional polymorphisms in NGF (rs6330) and NGFR (rs2072446 and rs734194) genes with ischemic stroke in an Armenian population.MethodsIn total, 370 unrelated individuals of Armenian nationality were enrolled in this study. Genomic DNA samples of patients and healthy controls were genotyped using polymerase chain reaction with sequence-specific primers.ResultsThe results obtained indicate that the minor allele of rs6330 (Pcorr = 2.4E-10) and rs2072446 (Pcorr = 0.02) are significantly overrepresented in stroke group, while the minor allele of rs734194 (Pcorr = 8.5E-10) was underrepresented in diseased subjects. Single nucleotide polymorphisms in NGF gene (rs6330) and NGFR gene (rs2072446 and rs734194) are associated with the disease. Furthermore, it was shown that the carriage of the NGF rs6330*T minor allele is associated with increased infarct volume and higher risk of recurrent stroke.ConclusionsIn conclusion, our findings suggest that the NGF rs6330*T and NGFR rs2072446*T minor alleles might be nominated as a risk factor for developing ischemic stroke and NGFR rs734194*G minor allele as a protective against this disease at least in Armenian population.

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“…Cerebral infarction (or ischaemic stroke), resulting from a blockage in the blood vessels supplying blood to the brain, or leakage outside the vessel walls, is the leading cause of acquired disability in adults and the second leading cause of dementia [ 1 ]. It constitutes the majority of cases of cerebrovascular accidents, and can be atherothrombotic or embolic [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Association between genetic polymorphisms of interleukins and cerebral infarction risk: a meta-analysis

et al. 2016

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Interleukins (ILs) are the most typical inflammatory and immunoregulatory cytokines. Evidences have shown that polymorphisms in ILs are associated with cerebral infarction risk. However, the results remain inconclusive. The present study was to evaluate the role of ILs polymorphisms in cerebral infarction susceptibility. Relevant case-control studies published between January 2000 and December 2015 were searched and retrieved from the electronic databases of Web of Science, PubMed, Embase and the Chinese Biomedical Database. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of association. A total of 55 articles including 12619 cerebral infarction patients and 14436 controls were screened out. Four ILs (IL-1, IL-6, IL-10 and IL-18) contained nine single nucleotide polymorphisms (SNPs; IL-1α −899C/T, IL-1β −511C/T and IL-1β +3953C/T; IL-6 −174G/C and −572C/G; IL-10 −819C/T and −1082A/G; IL-18 −607C/A and −137G/C). Our result showed that IL-1α −899C/T and IL-18 −607C/A (under all the genetic models), and IL-6 −572C/G (under the allelic model, heterogeneity model and dominant model) were associated with increased the risk of cerebral infarction (P<0.05). Subgroup analysis by ethnicity showed that IL-6 −174G/C polymorphism (under all the five models) and IL-10 −1082A/G polymorphism (under the allelic model and heterologous model) were significantly associated with increased the cerebral infarction risk in Asians. Other genetic polymorphisms were not related with cerebral infarction susceptibility under any genetic models. In conclusion, IL-1α −899C/T, IL-6 −572C/G and IL-18 −607C/A might be risk factors for cerebral infarction development. Further studies with well-designed and large sample size are still required.

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Ischemic stroke as a complex polygenic disease

Cited by 19 publications

References 165 publications

Association of miR-146a, miR-149, miR-196a2, miR-499 gene polymorphisms with ischemic stroke in a Chinese people

Association of miR-146a, miR-149, miR-196a2, miR-499 gene polymorphisms with ischemic stroke in a Chinese people

Involvement of polymorphisms of the nerve growth factor and its receptor encoding genes in the etiopathogenesis of ischemic stroke

Association between genetic polymorphisms of interleukins and cerebral infarction risk: a meta-analysis

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