DNA Hypomethylation of the MPO Gene in Peripheral Blood Leukocytes Is Associated with Cerebral Stroke in the Acute Phase

Бушуева, О. Ю.; Барышева, Е.М.; Марков, А. В.; Белых, А. Е.; Koroleva, I A; Чуркин, Е.О.; Polonikov, Alexey; Иванов, В. П.; Nazarenko, M. S.

doi:10.1007/s12031-021-01840-8

Cited by 9 publications

(9 citation statements)

References 72 publications

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“…The previous studies have already revealed genetic markers associated with the development of IS [6,7,8], as well as related phenotypes/risk factors, such as hypertension [9,10,11], atherosclerosis [12,13], and thrombosis [14]. However, despite the large number of studies conducted in the world, the molecular mechanisms of IS development remain poorly understood.…”

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confidence: 99%

C9orf16 (BBLN) gene, encoding a member of Hero proteins, is a novel marker in ischemic stroke risk

Kobzeva¹,

Shilenok²,

Белых³

et al. 2022

RR. in B.

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Background: Ischemic stroke (IS) is the leading cause of death and disability worldwide. Chaperone proteins protect brain cells from the ischemic damage by restoring the structures of damaged proteins. Chaperone C9orf16 (also known as BBLN) belongs to the class of heat-resistant obscure (HERO) proteins, characterized by the ability to stabilize various proteins, suppress neurotoxicity and reduce proteotoxic stress. In this regard, it may play a potentially significant role in the risk of development and clinical manifestations of IS. The aim of the study: To investigate an association between a single nucleotide polymorphism rs2900262 in the gene encoding C9orf16 and predisposition to IS. Materials and methods: A total of 897 patients with IS and 1140 healthy controls were recruited for the study. Genotyping was done using a probe-based genotyping assay. Multiple logistic regression analysis was performed to evaluate the associations of the rs2900262 genotypes with the risk of IS and ischemic events. Dominant, recessive and additive models of associations of genotypes were analyzed. Adjustment for sex, age, and smoking was done throughout. Benjamini-Hogberg false-discovery rate was used to correct for multiple comparisons. Results: The rs2900262*T allele was found to be associated with the increased risk of IS exclusively in females (dominant model: OR=1.74, 95% CI=1.07-2.82, PFDR=0.042; additive model: OR=1.69, 95% CI=1.06-2.71, PFDR=0.042). Additional analysis showed that the rs2900262*T is associated with the increased risk of IS in smokers only (dominant model: OR=1.92, 95% CI=1.09-3.37, PFDR=0.042; additive model: OR=1.79, 95%CI=1.04-3.08, PFDR=0.042). Also, we demonstrated that C/T-T/T genotype carriers exhibit an earlier manifestation of IS (59.53±1.12 years) compared to the C/C genotype carriers (61.63±0.4 years); mean difference=-1.98; 95% CI=-3.61 – -0.36; PFDR=0.026. Conclusion: This study is the first in the world to demonstrate the possible contribution of the rs2900262 C9orf16 gene polymorphism to the risk of ischemic stroke.

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confidence: 99%

C9orf16 (BBLN) gene, encoding a member of Hero proteins, is a novel marker in ischemic stroke risk

Kobzeva¹,

Shilenok²,

Белых³

et al. 2022

RR. in B.

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“…Several studies have reported that specific DNA methylation levels are associated with ischemic stroke [25]. For example, Bushueva et al assessed DNA hypomethylation in the MPO gene that is associated with cerebral stroke [26]. Another study by Li et al identified that genes involved in the homocysteine metabolic pathway-methylenetetrahydrofolate dehydrogenase 1, cystathionine β-synthase, and dihydrofolate reductase-were hypomethylated in patients with stroke as compared with patients with hypertension [27].…”

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confidence: 99%

Association of CYP26C1 Promoter Hypomethylation with Small Vessel Occlusion in Korean Subjects

Lee

Kim

Yim

et al. 2021

Genes

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The risk factors for stroke, a fatal disease, include type two diabetes, hypertension, and genetic influences. Small vessel occlusion (SVO) can be affected by epigenetic alterations, but an association between SVO and the methylation of cytochrome P450 family 26 subfamily C member 1 (CYP26C1) has not been identified. In this study, we measured the level of DNA methylation in the CYP26C1 promoter and the 5′ untranslated region of 115 normal subjects and 56 patients with SVO in Korea. The DNA methylation level of each subject was measured by bisulfite amplicon sequencing, and statistical analysis was performed using the general linear model or Pearson’s correlation. The average level of DNA methylation was markedly lower in patients with SVO than in normal subjects (20.4% vs. 17.5%). We found that the methylation of CYP26C1 has a significant positive correlation with blood parameters including white blood cells, hematocrit, lactate dehydrogenase, and Na+ in subjects with SVO. We predicted that binding of RXR-α and RAR-β might be affected by CYP26C1 methylation at CpG sites −246–237 and −294–285. These findings suggest that CYP26C1 methylation in the promoter region may be a predictor of SVO.

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“…IS is considered a multifactorial disease due to the involvement of genetic and environmental factors [ 2 ]. A lot of studies have been done to evaluate the genetic nature of IS [ 3 , 4 , 5 , 6 , 7 ] and IS-related modifiable risk factors, like hypertension [ 8 , 9 ], atherosclerosis [ 10 , 11 ], thrombosis [ 12 ]. However, disclosure of genetic correlates of IS remains an important task on the way to predicting and fighting the disease.…”

Section: Introductionmentioning

confidence: 99%

Association between HSPA8 Gene Variants and Ischemic Stroke: A Pilot Study Providing Additional Evidence for the Role of Heat Shock Proteins in Disease Pathogenesis

Kobzeva

Soldatova

Stetskaya

et al. 2023

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HSPA8 is involved in many stroke-associated cellular processes, playing a pivotal role in the protein quality control system. Here we report the results of the pilot study aimed at determining whether HSPA8 SNPs are linked to the risk of ischemic stroke (IS). DNA samples from 2139 Russians (888 IS patients and 1251 healthy controls) were genotyped for tagSNPs (rs1461496, rs10892958, and rs1136141) in the HSPA8 gene using probe-based PCR. SNP rs10892958 of HSPA8 was associated with an increased risk (risk allele G) of IS in smokers (OR = 1.37; 95% CI = 1.07–1.77; p = 0.01) and patients with low fruit and vegetable consumption (OR = 1.36; 95% CI = 1.14–1.63; p = 0.002). SNP rs1136141 of HSPA8 was also associated with an increased risk of IS (risk allele A) exclusively in smokers (OR = 1.68; 95% CI = 1.23–2.28; p = 0.0007) and in patients with a low fruit and vegetable intake (OR = 1.29; 95% CI = 1.05–1.60; p = 0.04). Sex-stratified analysis revealed an association of rs10892958 HSPA8 with an increased risk of IS in males (risk allele G; OR = 1.30; 95% CI = 1.05–1.61; p = 0.01). Thus, SNPs rs10892958 and rs1136141 in the HSPA8 gene represent novel genetic markers of IS.

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DNA Hypomethylation of the MPO Gene in Peripheral Blood Leukocytes Is Associated with Cerebral Stroke in the Acute Phase

Cited by 9 publications

References 72 publications

C9orf16 (BBLN) gene, encoding a member of Hero proteins, is a novel marker in ischemic stroke risk

C9orf16 (BBLN) gene, encoding a member of Hero proteins, is a novel marker in ischemic stroke risk

Association of CYP26C1 Promoter Hypomethylation with Small Vessel Occlusion in Korean Subjects

Association between HSPA8 Gene Variants and Ischemic Stroke: A Pilot Study Providing Additional Evidence for the Role of Heat Shock Proteins in Disease Pathogenesis

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