Promoter Polymorphism (-308G/A) of Tumor Necrosis Factor-Alpha (TNF-α) Gene and Asthma Risk: An Updated Meta-Analysis.

Background and Aims: The relationship between the promoter polymorphism (-308G/A) of the tumor necrosis factor-alpha (TNF-α) gene and the susceptibility to asthma has been tested in several studies. However, the results have been inconsistent. Therefore, we performed an updated meta-analysis to evaluate the relationship between this promoter polymorphism of the TNF-α gene and the risk of asthma. Methods: Fifty case-control studies were included in this meta-analysis which provided 17,937 controls and 9961 asthma patients. The pooled p-value, odds ratio (OR), and 95% confidence interval (95% CI) were used to investigate the strength of the association of this polymorphism of the TNF-α gene with the risk of asthma. The meta-analysis was carried out by Comprehensive Meta-Analysis software. Results: The results of our meta-analysis revealed that the TNF-α polymorphism (-308, G/A) was strongly associated with the risk of asthma (p < 0.05 in the allelic, dominant, and recessive models, respectively). In further analyses, based on age group and ethnicity, we observed this association for all subpopulations examined (p < 0.05 in allelic, dominant, and recessive models, respectively). Conclusion: This large-scale meta-analysis supports a strong association between the TNF-α gene promoter polymorphism (-308G/A) and the development to asthma in both children and adults.

The Effects of Korea Red Ginseng on Inflammatory Cytokines and Apoptosis in Rat Model with Chronic Nonbacterial Prostatitis.

Chronic prostatitis typically occurs in aging men, and its symptoms include frequent and painful urination. In recent study, several studies have shown that Korean red ginseng (KRG) can be used in the prevention and treatment of various diseases. The objective of this study is to investigate whether KRG can play a role in repressing the development of chronic nonbacterial prostatitis (CNP) in male Wistar rats. To induce CNP, rats were castrated and beta-estradiol (0.25 mg/kg) was subcutaneously (s.c.) injected daily. 7-week-old male Wistar rats were divided into 5 groups (the normal group, CNP group, positive group, and KRG group (0.25g/kg) and another KRG (0.50g/kg) group. After 4 weeks, all rats were sacrificed and their prostate and serum were analyzed. Compared to the positive group, the KRG groups (0.25g/kg and 0.50g/kg) showed similar protective properties on CNP based on the histopathologic morphology of the prostate and the inflammation cytokines in the prostate tissue. Also, results of the immunohistochemistry staining showed that expression levels of vascular endothelial growth factor A (VEGFA), interleukin 6 (IL6), interleukin 1 beta (IL-1ß), tumor necrosis factor (TNF-alpha), and cytochrome c oxidase subunit II (COX2) were also decreased in KRG group (0.25g/kg) and KRG group (0.50g/kg). These results suggested that KRG inhibited the development of CNP and might a useful herbal treatment or functional food for CNP.

Effects of Panax ginseng on the nerve growth factor expression in testosterone induced benign prostatic hyperplasia.

The prostatic hyperplasia in benign prostatic hyperplasia (BPH) leads to obstructive micturition symptoms. Previous studies showed that pontine micturition center (PMC), ventrolateral periaqueductal gray (vlPAG), and medial preopticnucleus (MPA) regions in the brain have been known to regulate the urinary bladder function. The present study shows the influences of Panax ginseng on nerve growth factor (NGF) expressions in PMC, vlPAG, and MPA regions in the brain. Wistar rats were used for the present study. The rats split into four groups; 4 groups (n = 6) in control group, BPH-induced group, BPH-induced and P. ginseng-treated group, and BPH-induced and finasteride-treated group. BPH in rats was induced by testosterone and the animals were evaluated for NGF expression in PMC, vlPAG, and MPA regions in the brain. The NGF expression was identified using immunohistochemistry (IHC). The NGF expression by IHC showed spots with dark brown color. In our results, NGF expressions in PMC, vlPAG, and MPA regions in the brainstem of the BPH-induced group showed increase than the control animal. These increased NGF expressions in three regions were decreased using treatment with P. ginseng (200 mg/kg). These results suggest that P. ginseng has therapeutic effects on the symptoms of BPH and is associated with the regulation of NGF expression in the brain. In conclusion, the administration of P. ginseng helps nerve growth factor activation.

BBOX1 is down-regulated in maternal immune-activated mice and implicated in genetic susceptibility to human schizophrenia.

Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorders such as bipolar disorder, autism, and schizophrenia in later life. Gamma-butyrobetaine hydroxylase (BBOX 1) is an enzyme responsible for the biosynthesis of l-carnitine, a key molecule in fatty acid metabolism. This cytosolic dimeric protein belongs to the dioxygenase family. In this study, we investigated whether BBOX 1 expression was related to psychiatric disorder in an animal model. We also conducted a case-control study using 284 schizophrenia patients and 409 controls with single-nucleotide polymorphisms (SNPs) in the 5'-near region of BBOX 1. BBOX 1 expression was increased in the medial frontal cortex of a mouse model of schizophrenia induced by maternal immune activation. Furthermore, the genotype and allele frequencies of two SNPs (rs7939644 and rs10767592) were significantly associated with schizophrenia susceptibility. Our results suggest that BBOX 1 might be associated with maternal immune activation and schizophrenia susceptibility. Therefore, it might be involved in the pathophysiology of schizophrenia.

Association Between Alcohol Consumption and Metabolic Syndrome in a Community-Based Cohort of Korean Adults.

BACKGROUND The relationship between alcohol consumption and metabolic syndrome (MetS) remains controversial. This study investigated the relationship between alcohol consumption and MetS components and prevalence. MATERIAL AND METHODS We analyzed 10 037 subjects (3076 MetS and 6961 non-MetS) in a community-based cohort. MetS was defined according to the ATP III Guidelines. Subjects were divided according to amount of alcohol consumption; non-drinker, very light (0.1-5.0 g/day), light (5.1-15.0 g/day), moderate (15.1-30.0 g/day), and heavy drinker (>30 g/day). Multiple logistic regression models were performed to estimate odds ratios (ORs) and confidence intervals (CIs). The analyses were performed in men and women separately. SPSS statistical software was used for analyses. RESULTS The prevalence of MetS in both males and females was associated with alcohol drinking status (p<0.0001). Amount of alcohol consumption (0.1-5.0 g/day) was significantly associated with lower prevalence of MetS in both genders compared to non-drinkers. Amount of alcohol consumption (>30.0 g/day) did not show a significant association with prevalence of MetS. However, alcohol consumption (>30.0 g/day) showed an association with glucose and HDL cholesterol among the components of MetS. CONCLUSIONS Our results indicate that alcohol drinking (0.1-5.0 g/day) contributed to decrease prevalence of MetS and components, including triglyceride and HDL cholesterol.

Association Between a Polymorphism in CASP3 and CASP9 Genes and Ischemic Stroke.

OBJECTIVE: To investigate whether the polymorphisms of CASP3 gene (rs4647602, intron A/C and rs1049216, UTR C/T) and CASP9 gene (rs1052576, Gln/Arg G/A and rs1052571, Ser/Val T/C) were associated with the development, and clinical severity of ischemic stroke and functional consequences after stroke. METHODS: Genomic DNA from 121 ischemic stroke patients and 201 healthy control subjects were extracted, and polymerase chain reaction products were sequenced. To investigate the association of polymorphisms and the development, and National Institutes of Health Stroke Scale (K-NIHSS), logistic regression models were analyzed. RESULTS: Polymorphism of the untranslational region of CASP3 (rs1049216, UTR C/T) has been associated with the development of ischemic stroke-in codominant1 model (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.29-0.88; p=0.017), in dominant model (OR, 0.57; 95% CI, 0.34-0.97; p=0.034), and in the overdominant model (OR, 0.50; 95% CI, 0.29-0.87; p=0.011). A missense SNP of CASP9 gene (rs1052571, Ser/Val T/C) was associated with the development of ischemic stroke (OR, 1.93; 95% CI, 1.05-3.55; p=0.034 in recessive model). CONCLUSION: These results indicate the possibility that CASP3 and CASP9 genes are markers for the development of ischemic stroke.

Human 8-oxoguanine DNA glycosylase gene polymorphism (Ser326Cys) and cancer risk: updated meta-analysis.

Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) has been reported to have a relationship with the risk of the development of various cancers. Many studies have described the influence of Ser326Cys polymorphism of the hOGG1 gene on cancer susceptibility. However, the results have remained inconclusive and controversial. Therefore, we performed a meta-analysis to more precisely determine the relationship between the hOGG1 polymorphism and the development of cancer.Electronic databases including PubMed, Embase, Google Scholar, and the Korean Studies Information Service System (KISS) were searched. The odds ratio (OR), 95% confidence interval (CI), and p value were calculated to assess the strength of the association with the risk of cancer using Comprehensive Meta-analysis software (Corporation, NJ, USA). The 127 studies including 38,757 cancer patients and 50,177 control subjects were analyzed for the meta-analysis.Our meta-analysis revealed that G allele of Ser326Cys polymorphism of the hOGG1 gene statistically increased the susceptibility of cancer (all population, OR = 1.092, 95% CI = 1.051-1.134, p < 0.001; in Asian, OR = 1.095, 95% CI = 1.048-1.145, p < 0.001; in Caucasian, OR = 1.097, 95% CI = 1.033-1.179, p = 0.002). Also, other genotype models showed significant association with cancer (p < 0.05, respectively).The present meta-analysis concluded that the G allele was associated with an increased risk of cancer. It suggested that the hOGG1 polymorphism may be a candidate marker of cancer.

Association Between Secretoglobin Family 3A Member 2 (SCGB3A2) Gene Polymorphisms and Asthma in a Korean Population.

BACKGROUND Secretoglobin family 3A member 2 (SCGB3A2) plays an important role in secreting lung surfactant protein, which is a downstream target of thyroid transcription factor. MATERIAL AND METHODS We investigated whether single-nucleotide polymorphisms (SNPs) of SCGB3A2 gene contribute to susceptibility to asthma. To explore this possible association, 2 promoter SNPs (rs6882292, 659 G/A and rs1368408, -112 G/A) and missense SNP (rs151333009, stop codon) were tested in SCGB3A2 gene in 101 asthma patients and 377 healthy control subjects. SNPStats was used to obtain odds ratio (OR), 95% confidence intervals (CI), and P value adjusted for age and sex as covariables. Logistic regression method in each model (dominant, recessive, and log-additive) was applied to analyze genetic data. RESULTS rs151333009 SNP showed a monomorphic genotype. Two promoter SNPs (rs6882292, -659 G/A and rs1368408, -112 G/A) showed significant association with asthma (rs6882292, OR=2.66, 95% CI=1.42-5.01, p=0.0033 in dominant model, OR=2.45, 95% CI=1.33-4.54, p=0.0055 in log-additive model; rs1368408, OR=1.59, 95% CI=1.02-2.49, p=0.041 in dominant model, OR=3.02, 95% CI=1.15-7.90, p=0.03 in recessive model, OR=1.63, 95% CI=1.63, 95% CI=1.12-2.37, p=0.012 in log-additive model). CONCLUSIONS These results suggest that the promoter SNPs (rs6882292 and rs1368408) of SCGB3A2 gene may contribute to susceptibility to asthma in a Korean population.

A herbal formula, comprising Panax ginseng and bee-pollen, inhibits development of testosterone-induced benign prostatic hyperplasia in male Wistar rats.

A recent study reported that Panax ginseng (P. ginseng) has a protective effect on the development of benign prostatic hyperplasia (BPH). KH053 is used as a new herbal prescription consisting of P. ginseng and bee-pollen. The present study aimed to investigate whether the KH053 has inhibition effects on the development of benign prostatic hyperplasia (BPH) using an animal model with testosterone induced BPH. The experiment was carried out in forty male Wistar 7 week old rats that were divided into four groups (control group, BPH group, positive group, and KH053 group). One group was used as the control and the three groups received subcutaneous injections of testosterone 20 mg/kg for 4 weeks to induce BPH. One of them received KH053 by oral gavage daily at doses of 200 mg/kg concurrently with the testosterone. The positive group received finasteride at a dose of 1 mg/kg with testosterone. After 4 weeks, all rats were sacrificed and analyzed for prostate weight, and growth factors. Results revealed that, compared to rats in the BPH group, KH053 showed that the prostate weight and dihydrotestosterone (DHT) levels in serum were significantly decreased and the decreases in hyperplasia in prostate were also observed. In addition, immunohistochemistry (IHC) also revealed that the protein expressions of growth factors [transforming growth factor ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF)] in prostate tissue were decreased in the KH053 group. In conclusion, these results suggest that KH053, comprising P. ginseng and bee-pollen, inhibits the development of BPH in Wistar rat model and might be used as functional food for BPH.

Association of promoter polymorphism -857C/T (rs1799724) in tumor necrosis factor gene with intracerebral hemorrhage in Korean males.

BACKGROUND AND PURPOSE: Tumor necrosis factor (TNF) has been shown to be involved in the pathogenesis of hemorrhagic stroke, having deleterious effects on cerebral arteries by promoting inflammation and apoptosis in vascular and immune cells. In this study, we investigated genetic association between TNF gene and intracerebral hemorrhage (ICH) in a Korean population. METHODS: Single nucleotide polymorphisms (SNPs) of TNF gene [-857C/T (rs1799724) and -308G/A (rs1800629)] were selected and genotyped using direct sequencing in 144 ICH patients and 455 control subjects. Genotype distribution and allele frequency were compared between cases and controls using logistic regression. RESULTS: -857C/T was significantly associated with ICH in log-additive [odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.14-2.24, p = 0.0081], and recessive models (OR = 3.25, 95% CI = 1.28-8.27, p = 0.016). The frequency of the -857TT genotype increased in ICH patients. Allele frequency analysis also showed that the -857T allele was associated with an increased risk of ICH (OR = 1.62, 95% CI = 1.15-2.30, p = 0.006). In the analysis according to the gender, we found that the association of -857C/T was gender-different. The -857C/T was significantly associated with ICH only in males (OR = 1.99, 95% CI = 1.24-3.19, p = 0.0043 in males; OR = 1.30, 95% CI = 0.76-2.22, p = 0.34 in females). CONCLUSION: These results suggest that promoter polymorphism of TNF gene, -857C/T, may be involved in the susceptibility of ICH in males.

Genetic Polymorphism of Angiotensin-Converting Enzyme and Chronic Obstructive Pulmonary Disease Risk: An Updated Meta-Analysis.

The relationship between polymorphism of the angiotensin I converting enzyme (ACE) gene and chronic obstructive pulmonary disease (COPD) has been examined in many previous studies. However, their results were controversial. Therefore, we performed a meta-analysis to evaluate the relationship between the ACE gene and the risk of COPD. Fourteen case-control studies were included in this meta-analysis. The pooled p value, odds ratio (OR), and 95% confidence interval (95% CI) were used to investigate the strength of the association. The meta-analysis was performed using comprehensive meta-analysis software. Our meta-analysis results revealed that ACE polymorphisms were not related to the risk of COPD (p > 0.05 in each model). In further analyses based on ethnicity, we observed an association between insertion/deletion polymorphism of the ACE gene and risk of COPD in the Asian population (codominant 2, OR = 3.126, 95% CI = 1.919-5.093, p < 0.001; recessive, OR = 3.326, 95% CI = 2.190-5.050, p < 0.001) but not in the Caucasian population (p > 0.05 in each model). In conclusion, the present meta-analysis indicated that the insertion/deletion polymorphism of the ACE gene may be associated with susceptibility to COPD in the Asian population but not in the Caucasian population. However, the results of the present meta-analysis need to be confirmed in a larger sample.

Promoter Polymorphism (-174, G/C) of Interleukin-6 and Arterial Thromboembolic Events: A Meta-Analysis.

BACKGROUND Ischemic stroke and myocardial infarction are fatal diseases and are among the top 10 causes of death in Korea, including arterial thromboembolic events. Many previous studies have described the function of interleukin-6 (IL-6) in arterial thromboembolic events and the association between promoter single-nucleotide polymorphism (SNP) (rs1800795; -174, G/C) of the IL-6 gene. However, these results were controversial. Therefore, we performed a meta-analysis to more precisely assess the association between the SNP of the IL-6 gene and susceptibility to arterial thromboembolic events. MATERIAL AND METHODS We used PubMed, Embase, Google Scholar, and Korean Studies Information Service System (KISS) electronic databases. Comprehensive Meta-analysis software (Corporation, NJ) was used to evaluate the relationship between rs1800795 SNP of IL-6 gene and risk of arterial thromboembolic events. Odds ratio (OR), 95% confidence interval (CI), and P value were also calculated. The 13 eligible studies were analyzed in the meta-analysis. RESULTS The present meta-analysis found that rs1800795 SNP of IL-6 gene is not significantly associated with susceptibility to arterial thromboembolic events (C allele vs. G allele, OR=1.04, 95% CI=0.91-1.19, P=0.619; CC vs. CG+GG, OR=1.09, 95% CI=0.91-1.31, P=0.364; CC+CG vs. GG, OR=0.97, 95% CI=0.78-1.21, P=0.763, respectively), and the SNP of IL-6 gene also did not show any significant association with ischemic stroke or myocardial infarction (P>0.05 in each model). CONCLUSIONS We found that rs1800795 SNP of IL-6 gene was not related to arterial thromboembolic events. However, further study will be needed to confirm these results.

Significant Association between Toll-Like Receptor Gene Polymorphisms and Posttransplantation Diabetes Mellitus.

BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is an important metabolic complication after renal transplantation. Activation of the innate immune system via toll-like receptors (TLRs) is implicated in the pathogenesis of insulin resistance and deficiency. Although links between diabetes, dysregulated innate immune responses, and the TLR signaling pathway have been reported, no study so far has investigated their associations with PTDM. In this study, we ascertained whether single nucleotide polymorphisms (SNPs) in TLRs are associated with PTDM in the Korea population. METHODS: A total of 305 patients who received renal transplants without previously diagnosed diabetes were included. We analyzed the association between PTDM development and 6 SNPs within 2 genes of TLR2, 1 gene of TLR4, and 3 genes of TRL6. RESULTS: Of 305 patients, PTDM developed in 51 patients (16.6%). Patients in the PTDM group were older than those in the non-PTDM group (45.56 ± 1.28 vs. 38.28 ± 0.71 years). Patients with PTDM had significantly higher allele frequency compared to those without PTDM for the TLR4 rs1927914*T, TLR6 rs3775073*A, TLR6 rs3821985*C, and TLR6 rs1039559*C alleles. Of the 6 SNPs, rs1927914 in the TLR4 gene and rs1039559 in the TLR6 gene were significantly associated with the development of PTDM after adjustment for age, gender, and tacrolimus usage. CONCLUSIONS: Our study demonstrates a significant association between SNPs rs1927914 in TLR4 and rs1039559 in TLR6 and PTDM in the renal transplantation recipient group. These data suggest that the activation of the innate immune system and inflammation via TLR activation might have an essential role in the pathogenesis of PTDM in renal transplantation.

Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot Case-Control Study in Korean Males.

The insulin-like growth factor (IGF) pathway is thought to play an important role in brain development. Altered levels of IGFs and their signaling regulators have been shown in autism spectrum disorder (ASD) patients. In this study, we investigated whether coding region single-nucleotide polymorphisms (cSNPs) of the insulin receptor substrates (IRS1 and IRS2), key mediators of the IGF pathway, were associated with ASD in Korean males. Two cSNPs (rs1801123 of IRS1, and rs4773092 of IRS2) were genotyped using direct sequencing in 180 male ASD patients and 147 male control subjects. A significant association between rs1801123 of IRS1 and ASD was shown in additive (p = 0.022, odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.46-0.95) and dominant models (p = 0.013, OR = 0.57, 95% CI = 0.37-0.89). Allele frequency analysis also showed an association between rs1801123 and ASD (p = 0.022, OR = 0.66, 95% CI = 0.46-0.94). These results suggest that IRS1 may contribute to the susceptibility of ASD in Korean males.

Association Between a Polymorphism (rs2071214) in Baculoviral IAP Repeat Containing 5 Gene (BIRC5) and Ischemic Stroke in Korean Population.

OBJECTIVE: To investigate whether baculoviral inhibitor of apoptosis (IAP) repeat containing 5 gene (BIRC5) polymorphisms are associated with the development and clinical phenotypes of ischemic stroke in Korea population. METHODS: We enrolled 121 ischemic stroke patients and 291 control subjects. Ischemic stroke patients were divided into subgroups according to the scores of National Institutes of Health Stroke Survey (<6 or ≥6) and Modified Barthel Index (<60 or ≥60). Single nucleotide polymorphisms (SNPs) of BIRC5 (rs3764383 and rs2071214) were selected and genotyped by direct sequencing for all subjects. Multiple logistic regression models (codominant 1 and 2, dominant, recessive, overdominant and log-additive) were used to estimate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. RESULTS: In analysis of stroke susceptibility, the genotype and allele frequencies of rs3764383 exhibited no difference between the control group and the ischemic stroke group. SNP rs2071214 was associated with ischemic stroke in the codominant (p=0.003), dominant (p=0.002), overdominant (p=0.005), and log-additive (p=0.008) models, respectively. The G allele frequency of rs2071214 was significantly (p=0.009) associated with susceptibility for ischemic stroke (OR, 1.57; 95% CI, 1.12-2.21). However, in the analysis for clinical phenotype, no SNP of the BIRC5 gene was found to be associated with ischemic stroke. CONCLUSION: These results suggest that a missense SNP (rs2071214) of BIRC5 may be associated with the development of ischemic stroke in the Korean population.

Interleukin-6 Receptor Polymorphisms Contribute to the Neurological Status of Korean Patients with Ischemic Stroke.

To investigate the contribution of the interleukin-6 receptor (IL-6R) gene single nucleotide polymorphisms (SNPs) to the neurological status of Korean patients with ischemic stroke (IS), two SNPs of the IL-6R gene (rs4845617, 5 UTR; rs2228144, Ala31Ala) were selected. IS patients were classified into clinical phenotypes according to two well-defined scores: the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index scores. There were 121 IS patients and 291 control subjects. The SNP rs4845617 significantly contributed to the neurological status of patients with IS (P = 0.011 in codominant model 2, P = 0.006 in recessive model, and P = 0.008 in log-additive model). Allele frequencies of rs4845617 and rs2228144 demonstrated no significant difference in IS patients and controls. The AG and GG haplotypes differed between the NIHSS 1 (NIHSS scores < 6) group and the NIHSS 2 (NIHSS scores ≥ 6) group in patients with IS (P = 0.014, P = 0.0024). These results suggest that rs4845617 of the IL-6R gene is associated with the neurologic status of Korean patients with IS.

Polymorphism of Nitric Oxide Synthase 1 Affects the Clinical Phenotypes of Ischemic Stroke in Korean Population.

OBJECTIVE: To investigate whether four single nucleotide polymorphisms (SNPs) rs2293054 [Ile734Ile], rs1047735 [His902His], rs2293044 [Val1353Val], rs2682826 (3'UTR) of nitric oxide synthase 1 (NOS1) are associated with the development and clinical phenotypes of ischemic stroke. METHODS: We enrolled 120 ischemic stroke patients and 314 control subjects. Ischemic stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ≥6) and Modified Barthel Index (MBI, <60 and ≥60). SNPStats, SNPAnalyzer, and HelixTree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. Multiple logistic regression models were performed to analyze genetic data. RESULTS: No SNPs of the NOS1 gene were found to be associated with ischemic stroke. However, in an analysis of clinical phenotypes, we found that rs2293054 was associated with the NIHSS scores of ischemic stroke patients in codominant (p=0.019), dominant (p=0.007), overdominant (p=0.033), and log-additive (p=0.0048) models. Also, rs2682826 revealed a significant association in the recessive model (p=0.034). In allele frequency analysis, we also found that the T alleles of rs2293054 were associated with lower NIHSS scores (p=0.007). Respectively, rs2293054 had a significant association in the MBI scores of ischemic stroke in codominant (p=0.038), dominant (p=0.031), overdominant (p=0.045), and log-additive (p=0.04) models. CONCLUSION: These results suggest that NOS1 may be related to the clinical phenotypes of ischemic stroke in Korean population.