Stroke In Koreans Research Articles

Current Perspectives on the Physiological Activities of Fermented Soybean-Derived Cheonggukjang.

Cheonggukjang (CGJ, fermented soybean paste), a traditional Korean fermented dish, has recently emerged as a functional food that improves blood circulation and intestinal regulation. Considering that excessive consumption of refined salt is associated with increased incidence of gastric cancer, high blood pressure, and stroke in Koreans, consuming CGJ may be desirable, as it can be made without salt, unlike other pastes. Soybeans in CGJ are fermented by Bacillus strains (B. subtilis or B. licheniformis), Lactobacillus spp., Leuconostoc spp., and Enterococcus faecium, which weaken the activity of putrefactive bacteria in the intestines, act as antibacterial agents against pathogens, and facilitate the excretion of harmful substances. Studies on CGJ have either focused on improving product quality or evaluating the bioactive substances contained in CGJ. The fermentation process of CGJ results in the production of enzymes and various physiologically active substances that are not found in raw soybeans, including dietary fiber, phospholipids, isoflavones (e.g., genistein and daidzein), phenolic acids, saponins, trypsin inhibitors, and phytic acids. These components prevent atherosclerosis, oxidative stress-mediated heart disease and inflammation, obesity, diabetes, senile dementia, cancer (e.g., breast and lung), and osteoporosis. They have also been shown to have thrombolytic, blood pressure-lowering, lipid-lowering, antimutagenic, immunostimulatory, anti-allergic, antibacterial, anti-atopic dermatitis, anti-androgenetic alopecia, and anti-asthmatic activities, as well as skin improvement properties. In this review, we examined the physiological activities of CGJ and confirmed its potential as a functional food.

Association of genetic variants of RNF213 with ischemic stroke risk in Koreans.

Large artery disease (LAD), cardioembolism (CE), and small vessel disease (SVD) are well-established causes of ischemic stroke. Although a founder variant of RNF213 has been regarded a genetic susceptibility for Moyamoya disease (MMD) and certain types of intracranial atherosclerotic stenosis (ICAS), correlations between RNF213 variants and ischemic stroke with SVD remain largely unknown. This study aimed to characterize the associations of four RNF213 polymorphisms (4448G>A, 4810G>A, 4863G>A, and 4950G>A) with ischemic stroke subtypes in Koreans. Genetic data from 529 stroke patients were analyzed and compared to 424 age- and sex-matched controls. Genetic variants of RNF213, as obtained from the Human Gene Mutation Database, were analyzed in the study subjects using the polymerase chain reaction restriction fragment length polymorphism assay. We investigated four single-nucleotide polymorphisms of RNF213 to elucidate their association with ischemic stroke [LAD, (n = 192), SVD (n = 145) and CE (n = 51)]. The RNF213 4950G>A genotype was observed more frequently in cerebral stroke patients and was more strongly associated with SVD than LAD (P = 0.014). RNF213 4448/4950 in combination with G-A was higher in SVD patients. However, the RNF213 4863/4950 allele combination was associated with increased risk of SVD and LAD. These results confirmed that RNF213 4950GA+AA variants were more frequent in ischemic stroke, especially in SVD, and that RNF213 G-G-G-A and G-G-G-A (4448/4810/4863/4950) haplotype sequences play a role in LAD and CE as well as SVD. Our data reported that theRNF2134950G>A genotypes and severalRNF213(4448/4810/4863/4950) haplotypes were associated with ischemic stroke in Koreans.

Bilirubin and Stroke Risk Using a Mendelian Randomization Design.

Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. The 14 single-nucleotide polymorphisms (SNPs) (<10-7) including rs6742078 of uridine diphosphoglucuronyl-transferase were selected from genome-wide association study of bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases. Weighted genetic risk score was calculated using 14 SNPs selected from the top SNPs. Both rs6742078 (F statistics=138) and weighted genetic risk score with 14 SNPs (F statistics=187) were strongly associated with bilirubin levels. Simultaneously, serum bilirubin level was associated with decreased risk of stroke in an ordinary least-squares analysis. However, in 2-stage least-squares Mendelian randomization analysis, no causal relationship between serum bilirubin and stroke risk was found. There is no evidence that bilirubin level is causally associated with risk of stroke in Koreans. Therefore, bilirubin level is not a risk determinant of stroke.

Moderate alcohol intake reduces risk of ischemic stroke in Korea.

We undertook a population-based, case-control study to examine a dose-response relationship between alcohol intake and risk of ischemic stroke in Koreans who had different alcoholic beverage type preferences than Western populations and to examine the effect modifications by sex and ischemic stroke subtypes. Cases (n = 1,848) were recruited from patients aged 20 years or older with first-ever ischemic stroke. Stroke-free controls (n = 3,589) were from the fourth and fifth Korean National Health and Nutrition Examination Survey and were matched to the cases by age (±3 years), sex, and education level. All participants completed an interview using a structured questionnaire about alcohol intake. Light to moderate alcohol intake, 3 or 4 drinks (1 drink = 10 g ethanol) per day, was significantly associated with a lower odds of ischemic stroke after adjusting for potential confounders (no drinks: reference; <1 drink: odds ratio 0.38, 95% confidence interval 0.32-0.45; 1-2 drinks: 0.45, 0.36-0.57; and 3-4 drinks: 0.54, 0.39-0.74). The threshold of alcohol effect in women was slightly lower than that in men (up to 1-2 drinks in women vs up to 3-4 drinks in men), but this difference was not statistically significant. There was no statistical interaction between alcohol intake and the subtypes of ischemic stroke (p = 0.50). The most frequently used alcoholic beverage was one native to Korea, soju (78% of the cases), a distilled beverage with 20% ethanol by volume. Our findings suggest that light to moderate distilled alcohol consumption may reduce the risk of ischemic stroke in Koreans.

Interplay between polymorphisms in the endothelial nitric oxide synthase (eNOS) gene and metabolic syndrome in determining the risk of ischemic stroke in Koreans

BackgroundEndothelial nitric oxide synthase (eNOS) gene variants are known to play a role in atherosclerotic development. However, whether interplay between eNOS polymorphisms and metabolic syndrome (MetS) affects ischemic stroke (IS) risk has yet to be discovered. We investigated whether the combined effects of eNOS polymorphisms and MetS influence ischemic stroke risk in Koreans. MethodsWe genotyped the eNOS −922A>G, −786T>C, 4a4b, and 894G>T polymorphisms in 531 IS cases and 502 controls using polymerase chain reaction-amplified DNA. We then investigated whether the presence of MetS and the number of MetS risk factors worked with eNOS polymorphisms to influence IS risk. ResultsIS patients had a significantly higher prevalence of MetS than controls [adjusted odds ratio (AOR)=2.943, 95% confidence interval (CI), 2.256–3.840, P<0.0001], and MetS prevalence did not differ between stroke subtypes. The 894GT+TT genotypes were positively associated with IS (AOR=1.670, 95% CI, 1.208–2.308, P=0.002), and the −786TC+CC genotypes showed co-morbidity with MetS (AOR=1.448, 95% CI, 1.401–2.015, P=0.028). Among subjects with three or more MetS risk factors, the highest AOR value (28.490, 95% CI, 3.162–256.688) was observed for the eNOS −786TC+CC genotypes. ConclusionsThe eNOS 894T allele and interplay between the eNOS −786C allele and MetS may predispose Koreans to IS.

Gene–environment interactions between methylenetetrahydrofolate reductase (MTHFR) 677C>T and metabolic syndrome for the prevalence of ischemic stroke in Koreans

Although metabolic syndrome (MS) is recognized as a risk factor for ischemic stroke, little is known about genetic variants that confer susceptibility to ischemic stroke among individuals with or without MS. This study was completed to investigate whether the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is associated with MS as a risk factor for ischemic stroke in the Korean population. The prevalence of MS was significantly higher in ischemic stroke patients than controls (adjusted odds ratio [AOR]=1.420; 95% confidence interval [CI]=1.017–1.982, P=0.040). MS prevalence was also significantly different between patients with subtypes of small-artery occlusion (AOR=1.707; 95% CI=1.081–2.695, P=0.022) and large-artery occlusion (AOR=1.661; 95% CI=1.089–2.534, P=0.019) versus controls. The frequencies of the MTHFR 677 TT genotype (AOR=3.001; 95% CI=1.487–6.057, P=0.002) and CT genotype (AOR=1.772; 95% CI=1.053–2.983, P=0.031) of the MS group, and for the CC genotype in those without MS were significantly different between the ischemic stroke patients and controls. The MTHFR 677C>T polymorphism was associated with a higher risk of MS among ischemic stroke patients in the Korean population.

Association of theAdiponectinGene Variations with Risk of Ischemic Stroke in a Korean Population

PurposeStroke is the second leading cause of death and a major cause of morbidity and mortality worldwide. Evidence of variations in adiponectin(AdipoQ) genes that are associated with ischemic stroke has not been consistent, and it is unclear whether the same loci contribute to these associations in the Korean population. Using a Korean population, we tested ischemic stroke-associated AdipoQ markers.Materials and MethodsIn a preliminary genome-wide association study using 320 250 k Affymetrix NSP chips, AdipoQ was found to be associated with ischemic stroke in Koreans. To study of AdipoQ, a further 673 ischemic stroke patients and 267 unrelated individuals without a history of stroke or transient ischemic attack were examined in a case-control study.ResultsSix polymorphisms (rs182052G > A, rs16861205G > A, rs822391T > C, rs822396A > G, rs12495941G > T and rs3774261A > G) that had a minor allele frequency of over 1% were strongly associated with stroke (p < 0.05). Two of these, rs822391T > C and rs822396A > G showed this association on both dominant and additive logistic regression analysis after adjusting for age and sex. The haplotypes ht 1 (AGGCGG and AAGTAG) were significantly associated with susceptibility to stroke.ConclusionOur findings show that polymorphisms in AdipoQ are associated with risk for ischemic stroke in the Korean population. This study lends further support to the putative role of AdipoQ in stroke.

Age and sex dependent genetic effects of neuropeptide Y promoter polymorphism on susceptibility to ischemic stroke in Koreans

Background In our previous study, the neuropeptide Y (NPY) C-399T promoter polymorphism (rs16147C > T) was identified as a risk factor for ischemic stroke in Koreans. In this study, we investigated whether age and sex modify the genetic effect of C-399T on susceptibility to ischemic stroke. Methods A total of 1,350 subjects (802 ischemic stroke patients, 548 healthy controls) were genotyped for C-399T using a primer extension method. The results were statistically analyzed for the genetic association of C-399T with ischemic stroke and clinical parameters. Results The TT genotype for C-399T was observed at a significantly lower frequency in stroke patients relative to control (CC + CT vs. TT, odds ratio [OR] = 0.578, 95% confidence interval [95% CI] = 0.360-0.927, P < 0.05). This trend was also observed in female (OR = 0.495, 95% CI = 0.240-1.022) and older subjects (y > 60, OR = 0.556, 95% CI = 0.304-1.018) with borderline statistical significance (P = 0.0571 and P = 0.0574, respectively). However, C-399T allele frequency was not different between controls and stroke patients in any groups. The C-399T polymorphism was found to be associated with body mass index and levels of some blood lipids. Conclusions The C-399T NPY promoter polymorphism should be considered a genetic risk factor for ischemic stroke in the older adult and female Korean populations.

Low level of n-3 polyunsaturated fatty acids in erythrocytes is a risk factor for both acute ischemic and hemorrhagic stroke in Koreans

Evidence suggesting an association between n-3 polyunsaturated fatty acids (PUFA) and stroke risk has been inconsistent, possibly because previous studies have not differentiated between different stroke types. The present study investigated the hypothesis that tissue levels of n-3 PUFA are positively associated with hemorrhagic stroke and negatively associated with ischemic stroke. We recruited 120 subjects for this case-control study, with 40 cases each of hemorrhagic stroke, ischemic stroke, and unaffected controls. Patients with a family history of hemorrhagic stroke had a significantly increased risk for hemorrhagic stroke. Omega-3 Index (20:5n3 + 22:6n3 in erythrocytes) and 22:6n3 were negatively (P < .01) associated with the risk of both hemorrhagic and ischemic stroke in multivariate analyses. Saturated fatty acids 16:0 and 18:0 were positively associated, whereas 18:2n6 and 18:3n6 were negatively (P < .05) associated with risk of ischemic stroke. Monounsaturated fatty acid, 18:1n9, increased (P = .03) the odds of hemorrhagic stroke. Omega-3 Index and docosahexaenoic acid were significantly lower in patients with both subtypes of hemorrhagic stroke, subarachnoid and intracerebral hemorrhage, but only in one subtype of ischemic stroke, small-artery occlusion. Saturated fatty acids 16:0 and 18:0 were significantly higher, but 20:4n6 was significantly lower, in patients with small-artery occlusion. Linoleic acid was significantly lower in patients with small-artery occlusion and large-artery atherosclerosis, whereas 18:1n9 was higher in both subgroups of hemorrhagic stroke. In conclusion, the results of our case-control study suggest that erythrocyte n-3 PUFA may protect against hemorrhagic stroke and ischemic stroke, particularly in the case of small-artery occlusion.

Decreased paraoxonase-1 activity is a risk factor for ischemic stroke in Koreans

Paraoxonase-1 (PON1) is an enzyme associated with HDL in blood and it is considered as an anti-oxidant factor due to its capability to prevent lipid oxidation. In vivo mouse studies also have shown that PON1 is one of the genetic risk factors contributing to atherosclerosis. In this study, we evaluated the serum PON1 activities of sex–age matched Korean healthy control and ischemic stroke patients, and investigated the association of PON1 activity with other metabolic parameters. Statistical analyses revealed that PON1 activity and HDL_cholesterol (HDL_C) in stroke patients were significantly decreased when compared with those of healthy control. Additionally, PON1 activity was negatively correlated with age, whereas it was positively correlated with HDL_C in a stroke group. Overall, the results of this study indicated that decreased serum PON1 activity should be considered as a risk factor for ischemic stroke in Koreans.