Cohort Profile Update: The Korean Genome and Epidemiology Study (KoGES).
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KoGES↗
Biomedical subjects
Hyun-Young Park
Publications and source records attributed to Hyun-Young Park.
Comparative whole-exome sequencing of ambulatory patients and transplant recipients with idiopathic dilated cardiomyopathy.
BACKGROUND: Idiopathic dilated cardiomyopathy (DCM) is a major cause of advanced heart failure and heart transplantation (HTx), yet the genetic correlates of progression to HTx and transplant-relevant arrhythmic phenotypes remain incompletely defined. We examined the genetics of idiopathic DCM in a Korean population, focusing on HTx/death and arrhythmic outcomes, to identify adverse outcome-linked genotype-phenotype associations. METHODS: Whole-exome sequencing was performed in 202 Korean patients with idiopathic DCM, including 56 HTx recipients and 146 ambulatory patients, and compared the findings with 1093 population-based controls. Genotype-phenotype correlations were analyzed for major clinical outcomes, including HTx, death, arrhythmias, and left ventricular functional recovery. RESULTS: Pathogenic/likely pathogenic variants were identified in 32% of patients (38% in HTx vs 30% in ambulatory patients). TTN was the most frequently affected gene overall (12%), but LMNA variants predominated in HTx recipients (20% vs 4%, p = 0.001). LMNA carriers showed substantially higher odds of HTx/death (OR 14.65, 95% CI 3.32-139.31; FDR p<0.001), and strong association with arrhythmias, including ventricular tachyarrhythmias and atrial fibrillation. Both missense and loss-of-function LMNA variants were associated with adverse outcomes. In contrast, TNNT2 variants were observed exclusively in ambulatory patients and identified a favorable functional-recovery phenotype, with a greater likelihood of LVEF recovery ≥10 percentage points (OR 6.03, 95% CI 1.52-28.71; FDR p = 0.016). CONCLUSIONS: LMNA variants mark a high-risk transplant-trajectory phenotype in Korean idiopathic DCM. Genetic testing may aid early identification and management of candidates for advanced HF therapies, including HTx and durable MCS.
dilated cardiomyopathy↗
Exploring novel MYH7 gene variants using in silico analyses in Korean patients with cardiomyopathy.
BACKGROUND: Pathogenic variants of MYH7, which encodes the beta-myosin heavy chain protein, are major causes of dilated and hypertrophic cardiomyopathy. METHODS: In this study, we used whole-genome sequencing data to identify MYH7 variants in 397 patients with various cardiomyopathy subtypes who were participating in the National Project of Bio Big Data pilot study in Korea. We also performed in silico analyses to predict the pathogenicity of the novel variants, comparing them to known pathogenic missense variants. RESULTS: We identified 27 MYH7 variants in 41 unrelated patients with cardiomyopathy, consisting of 20 previously known pathogenic/likely pathogenic variants, 2 variants of uncertain significance, and 5 novel variants. Notably, the pathogenic variants predominantly clustered within the myosin motor domain of MYH7. We confirmed that the novel identified variants could be pathogenic, as indicated by high prediction scores in the in silico analyses, including SIFT, Mutation Assessor, PROVEAN, PolyPhen-2, CADD, REVEL, MetaLR, MetaRNN, and MetaSVM. Furthermore, we assessed their damaging effects on protein dynamics and stability using DynaMut2 and Missense3D tools. CONCLUSIONS: Overall, our study identified the distribution of MYH7 variants among patients with cardiomyopathy in Korea, offering new insights for improved diagnosis by enriching the data on the pathogenicity of novel variants using in silico tools and evaluating the function and structural stability of the MYH7 protein.
Humans↗
Association of RAGE gene polymorphisms with coronary artery disease in the Korean population.
BACKGROUND AND OBJECTIVES: AGEs (advanced glycation end products)-RAGE (receptor for advanced glycation end products) interaction in vessel wall may lead to inflammation, smooth muscle cell proliferation and extracellular matrix production, culminating in exaggerated intimal hyperplasia and restenosis. We focused on the putative association of five candidate RAGE gene polymorphisms on the risk of coronary artery disease in the Korean population. METHODS: A total of 1555 male patients who underwent coronary angiography were enrolled in the study; 805 patients (mean age: 53.18+/-9.74 years) had normal coronary artery and 750 patients (mean age: 55.73+/-8.31 years) had significant coronary artery disease. Among the coronary artery disease patients, 269 had single-vessel disease (35.87%), 242 had two-vessel disease (32.27%) and 239 had three-vessel disease (31.87%). The genotypes of RAGE were determined by the methods of single base extension with amplifying primers and probes for TaqMan. Genotype analysis was performed on five single nucleotide polymorphisms of the RAGE gene, namely -443T>C, -388T>A, -257G>A, +557G>A and +1704G>T. Analysis for the association with coronary artery disease was performed. RESULTS: Analysis of four single nucleotide polymorphisms, except +557G>A (G82S), with regard to the association with coronary artery disease was not significant. Only the +557 gene allele (G/A) showed significant association with coronary artery disease (coronary artery disease vs. normal; G allele: 0.87 vs. 0.84, A allele: 0.13 vs. 0.16, P=0.0326). The +557G>A (G82S) showed strong tendency of association with coronary artery disease (coronary artery disease vs. normal; GG: 75.2 vs. 69.8%, GA: 23.2 vs. 28.6%, AA: 1.6 vs. 1.6%, P=0.0524). The presence of AA or GA genotype, assuming codominant effect of the A allele, was independently associated with decreased risk of coronary artery disease when controlled for age, body mass index, smoking and diabetes mellitus [odds ratio=0.749 (95% confidence interval, 0.579-0.969), P=0.0280]. Subgroup analysis demonstrated the significant protective effect of AA or GA genotype in nondiabetic patients as well [odds ratio=0.741 (0.570-0.962), P=0.0244]. CONCLUSIONS: The results of this large population study demonstrate that the AA/GA genotypes of the RAGE +557G>A polymorphism are associated with a significantly decreased risk of significant coronary artery disease. Other polymorphisms of RAGE were not significantly associated with the risk of coronary artery disease in this study population.
Asian People↗
Association of RAGE gene polymorphisms with in-stent restenosis in non-diabetic Korean population.
BACKGROUND: Interaction between advanced glycosylation end products (AGEs) and receptor for AGEs (RAGE) in vessel wall may lead to inflammation, smooth muscle cell proliferation, and extracellular matrix production, culminating in exaggerated intimal hyperplasia and restenosis. We investigated the possibility that single nucleotide polymorphisms of the genes encoding RAGE are associated with in-stent restenosis after coronary stenting. METHODS: Our study included 334 consecutive non-diabetic male patients with symptomatic coronary artery disease who underwent bare metal stent implantation. Follow-up angiography was performed in 297 patients (88.9%), 6 months after intervention. We screened -1106T-->C, -443T-->C, -388T-->A, -257G-->A, +557G-->A and +1704G-->T RAGE polymorphisms in these patients. Genotyping was performed by single base extension with amplifying primers and probes for TaqMan. RESULTS: A total of 355 target lesions were evaluated, in 297 patients. There was no significant association of the -1106T-->C, -443T-->C, -388T-->A, -257G-->A, +557G-->A or +1704G-->T polymorphisms with in-stent restenosis after coronary artery stenting. We did not observe a significant difference between the genotype distributions and the rates of angiographic restenosis between the polymorphisms. In a multivariate analysis of angiographic restenosis, we examined the possible influence of the baseline, lesion-related, and procedural variables. After adjustment for these potentially confounding factors, the multivariate analysis did not reveal an association of polymorphism with angiographic restenosis. CONCLUSION: Our observation suggests that the RAGE gene polymorphism is not associated with in-stent restenosis after coronary artery stenting in non-diabetic patients in the Korean population.
Angioplasty, Balloon, Coronary↗
Preconditioning with low concentration NO attenuates subsequent NO-induced apoptosis in vascular smooth muscle cells via HO-1-dependent mitochondrial death pathway.
Nitric oxide (NO) signaling pathways are important in both the maintenance of vascular homeostasis and disease progression. Overproduction of NO has been associated with ischemia/reperfusion (I/R) injury. Growing evidences suggest that NO preconditioning has cytoprotective effects against I/R injury. However, the mechanism with which NO mediates these effects remains to be elucidated. The purpose of this study was to examine the mechanism of how NO preconditioning inhibits subsequent NO-induced apoptosis in vascular smooth muscle cells (VSMC), specifically focusing on heme oxygenase-1 (HO-1). According to our data, sodium nitroprusside (SNP) increased HO-1 expression in a concentration dependent manner. Preconditioning with low concentration SNP (0.3mM) inhibited subsequent high concentration SNP (1.5mM)-induced apoptosis, and this effect was reversed by the HO-1 inhibitor SnPP. Low concentration SNP-mediated protection involved p38 kinase inactivation and increased Bcl-2 expression. Furthermore, mitochondrial membrane potential was concomitantly increased with decreased expressions of Bax, Apaf-1, and activity of caspase-3, which was reversed by SnPP treatment. Our results show that low concentration SNP preconditioning suppresses subsequent high concentration SNP-induced apoptosis by inhibiting p38 kinase and mitochondrial death pathway via HO-1-dependent mechanisms in VSMC.
Animals↗
PPARgamma activation induces CD36 expression and stimulates foam cell like changes in rVSMCs.
The purpose of the present study was to determine the role of peroxisome proliferator-activated receptor gamma (PPARgamma) activation in smooth muscle cell (SMC) derived form cell formation. Wild and mutant type PPARgamma were delivered by adenovirus then activated with troglitazone. The result of Oil Red O staining and FACS analysis showed that PPARgamma activation induced lipid accumulation in rVSMCs. Furthermore, PPARgamma activation reduced SMC marker genes such as alpha-actin while induced adipocyte differentiation marker genes and lipid metabolism-related genes as evidenced by RT-PCR and fluorescent immunocytochemistry. All these data demonstrate that PPARgamma activation can drive foam cell like change in rVSMCs. Our results strongly suggest that PPARgamma expression induces CD36 expression and adipocyte differentiation gene activation in the process of atherosclerosis and might be one of the crucial events in SMC derived foam cell formation.
ATP Binding Cassette Transporter 1↗
Troglitazone inhibits endothelial cell proliferation through suppression of casein kinase 2 activity.
Troglitazone, an agonist of peroxisome proliferator activated receptor gamma (PPARgamma), has been reported to inhibit endothelial cell proliferation by suppressing Akt activation. Recently, it has been also proposed that phosphatase and tensin homolog deleted from chromosome 10 (PTEN) plays an important role in such effect of troglitazone. However, the mechanism of how troglitazone regulates PTEN remains to be elucidated. We therefore investigated the effects of troglitazone on casein kinase 2 (CK2), which is known to negatively regulate PTEN activity. Troglitazone significantly inhibited serum-induced proliferation of HUVEC in a concentration dependent manner. Serum-induced Akt and its downstream signaling pathway activation was attenuated by troglitazone (10 microM) pretreatment. The phosphorylation of PTEN, which was directly related to Akt activation, was decreased with troglitazone pretreatment and was inversely proportional to CK2 activity. DRB, a CK2 inhibitor, also showed effects similar to that of troglitazone on Akt and its downstream signaling molecules. In conclusion, our results suggest that troglitazone inhibits proliferation of HUVECs through suppression of CK2 activity rendering PTEN to remain activated, and this effect of troglitazone in HUVECs seems to be PPARgamma independent.
Casein Kinase II↗
The applicability of the Asian modified criteria of the metabolic syndrome in the Korean population.
BACKGROUND: We compared the metabolic profiles and risk of coronary artery disease (CAD) in Koreans with non-diabetic metabolic syndrome (MetS). [We applied four criteria of MetS: the NCEP criteria, the Asian modified NCEP (a-NCEP) criteria, the WHO criteria and the Asian modified WHO (a-WHO).] METHODS: The study group composed of 2724 subjects enrolled in the cardiovascular genome center. There were 728 patients with significant CAD. The different criteria of the MetS were applied for the study population. RESULTS: Among the 2724 participants, 522 (19.2%) met the NCEP criteria, 796 (29.2%) met the a-NCEP criteria, 361 (13.3%) met the WHO criteria and 576 (21.1%) met the a-WHO criteria. The clinical parameters, lipid profile, apoA1 and apoB level were not different between the participants classified as MetS by using the different criteria. The odds ratio for CAD prediction were not significantly different according to the metabolic criteria (odd ratio: 1.755 [95% CI: 1.423-2.163] in NCEP criteria, 2.120 [1.763-2.549] in a-NCEP criteria, 1.854 [1.466-2.343] in WHO criteria, 2.205 [1.810-2.687] in a-WHO criteria). The serum level of apoA1 and apoB showed strong correlations with MetS classified by all criteria and the HOMA index and insulin level showed better correlations with WHO-MetS criteria. CONCLUSIONS: All the MetS criteria showed similar metabolic profiles and all four criteria had similar predictive value for CAD. Conventional MetS criteria, applied to the non-diabetic Asian population, may underestimate the population at risk. Our data suggests that the Asian modified criteria will decrease the risk for underdiagnosis while demonstrating similar metabolic profiles and CAD risk compared to the conventional criteria.
Coronary Artery Disease↗
Mutational spectrum of type I collagen genes in Korean patients with osteogenesis imperfecta.
Mutations in the type I collagen genes COL1A1 and COL1A2 are responsible for the dominantly inherited connective tissue disorder osteogenesis imperfecta (OI). The severity of OI is diverse, ranging from perinatal lethality to a very mild phenotype that is characterized by normal stature and the absence of deformities. Although there have been several studies on the mutational spectra of COL1A1 and/or COL1A2 in Western populations, very few cases have been reported from Asia. In this study, we investigated 67 unrelated Korean probands with OI and used nucleotide sequence analysis to detect COL1A1 and COL1A2 mutations. Thirty-five different mutations were identified in the two genes, including 24 novel mutations. Among the 35 kinds of detected mutations, 15 were glycine substitutions (seven in COL1A1 and eight in COL1A2), one was a nonsense mutation, four were frameshift mutations in COL1A1, three were in-frame duplications in COL1A2, and 12 were splice site mutations (seven in COL1A1 and five in COL1A2). Until now, mutations in the COL1A1 and COL1A2 genes known to cause OI were unique and rarely repeated in other families. Interestingly, the c.982G>A (p.Gly328Ser) mutation in COL1A2 was found recurrently and was the causative mutation in five independent OI probands. Haplotype analysis of the COL1A2 gene revealed that four probands from five independent OI probands with c.982G>A (p.Gly328Ser) had a common haplotype. Our clinical data showed the heterogeneity even within a specific genotype, which suggested the complex expression of this disease.
Adolescent↗
Interaction between -786TC polymorphism in the endothelial nitric oxide synthase gene and smoking for myocardial infarction in Korean population.
BACKGROUND: Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) mediates endothelium-dependent vasodilation and antithrombotic action. Controversial results regarding the association of eNOS gene polymorphisms with myocardial infarction (MI) have been reported. METHODS: A total of 932 individuals living in Seoul and the suburb, Korea, were randomly selected. Genomic DNA was prepared from blood leukocytes. A GT missense mutation in exon 7 (894GT) was screened using PCR-RFLP analysis. The genotypes of 3 mutations (-786TC, -922AG, and -1468TA) in the 5'-flanking region were determined by a minisequencing protocol (SNaPshot), respectively. RESULTS: Pair-wise linkage analysis revealed that 3 mutations of -786TC, -922AG, and -1468TA were completely linked with each other (mid R:D'mid R:=1, r(2)=0.96-1.0). Furthermore, each of these mutant alleles (-786C, -922G, or -1468A), but not 894T allele, was associated with the risk of MI. Multiple logistic regression analysis revealed that each of these mutant alleles was a predictive independent risk factor for the risk of MI (odds ratio, 1.69 for dominant effects, P<0.05) after age and sex adjustments. Smoking further increased the odds ratio by 2.04 for the risk of MI when it was combined with the mutant alleles. CONCLUSION: Each of 3 mutations (-786TC, -922AG, or -1468TA) in the 5'-flanking region of eNOS gene may play a role in the pathogenesis of MI in Korean population, and also provides an evidence for a significant interaction between these mutations and smoking.
Aged↗
Trichostatin A exacerbates atherosclerosis in low density lipoprotein receptor-deficient mice.
OBJECTIVE: Histone acetylation has been shown to be involved in expression of a restricted set of cellular genes including various proinflammatory molecules. We aimed to investigate the relationship between histone acetylation and atherosclerosis. METHODS AND RESULTS: In low-density lipoprotein (LDL) receptor-deficient (Ldlr(-/-)) mice fed an atherogenic diet for 4 or 8 weeks, trichostatin A (TSA), a specific histone deacetylase inhibitor, exacerbated atherosclerosis without alteration on plasma lipid profiles. When we assayed the effects of TSA on expressions of oxidized LDL (oxLDL) receptors on RAW264.7 macrophage, we found that TSA increased CD36 mRNA and protein, as well as cell surface expression of CD36. TSA also increased acetylation at the CD36 promoter region. The uptake of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine percholate (Dil)-labeled oxLDL was enhanced in RAW264.7 macrophage by TSA. Furthermore, TSA treatment increased CD36 mRNA expression in aorta, and SRA, tumor necrosis factor (TNF)-alpha, and vascular cell adhesion molecule-1 (VCAM-1) were also elevated, whereas IL-6 and IL-1beta expressions were decreased. CONCLUSIONS: Our findings suggest that histone acetylation could play some role in atherogenesis by modulating expressions of oxLDL receptor and some proatherogenic genes. Therefore, our results indicate that increased histone acetylation may affect the progress of atherosclerosis.
Acetylation↗
Berberine inhibits rat vascular smooth muscle cell proliferation and migration in vitro and improves neointima formation after balloon injury in vivo. Berberine improves neointima formation in a rat model.
Berberine, an alkaloid isolated from Chinese medicinal herbs, long been known for its anti-microbial activity and used to treat various infectious disorders in traditional Chinese medicine. In the present study, we have tested the hypothesis that berberine could inhibit vascular smooth muscle cell (VSMC) proliferation as it did in endothelial cells or cancer cells. Our results show that berberine significantly inhibits growth factor, mainly angiotensin II (AngII) and heparin binding epidermal growth factor (HB-EGF), induced VSMC proliferation and migration in vitro, and this effect is achieved by delaying or partially suppressing activation of Akt pathway rather than ERK pathway. Furthermore, we have examined its effect in vivo using a rat carotid artery injury model. A 28 days of chronic berberine treatment using an osmotic pump (100 microg kg(-1)d(-1), 2 weeks before and 2 weeks after the injury) improved neointima formation. The Neointima/Media ratio for control group and berberine treated group were 1.14+/-0.11 and 0.85+/-0.06 (p<0.05), respectively, and the reduction was approximately 25%. The result of the present study suggests a possibility of berberine being a potent agent to control restenosis after balloon angioplasty and warrants further study to gain a more complete understanding of its underlying mechanisms at a cellular level.
Angioplasty, Balloon↗
Endothelial nitric oxide synthase gene is associated with vessel stenosis in Korean population.
BACKGROUND: Nitric oxide (NO) produced by endothelial NO synthase (eNOS) mediates endothelium-dependent vasodilation and antithrombotic action. Controversial results regarding the association of eNOS gene polymorphisms with vessel stenosis have been reported. METHODS: Age- and sex-matched 932 individuals (656 subjects having 1-, 2-, and 3-stenosed vessels and 276 controls without stenosis) living in Seoul and surrounding suburbs were selected. A GT missense mutation in exon 7 (894GT) was screened using PCR-restriction fragment length polymorphism analysis. The genotypes of a 27-bp insertion/deletion in intron 4 (eNOS4b/a) and a TC mutation in promoter region of -786 (-786TC) were determined by the banding pattern on gel electrophoresis and a commercially available minisequencing protocol (SNaPshot), respectively. RESULTS: The eNOS4a allele was highly linked to the -786C allele (r=0.93, P<0.0001) while there was no linkage between eNOS4a allele and 894T allele or between 894T allele and -786C allele. Furthermore, 894T allele, but not eNOS4a (-786C) allele, was associated with the presence, but not the number, of stenosed vessels (odds ratio=1.57 for dominant effect of the T allele, P<0.05, and 1.49 for additive effect, P<0.05). Multiple logistic regression analysis revealed that 894T allele and hypertension were predictive independent risk factors for the presence of vessel stenosis. CONCLUSION: Our data suggest that eNOS gene polymorphisms may play an important role in the pathogenesis of vessel stenosis in Korean population.
Aged↗
Small-diameter blood vessels engineered with bone marrow-derived cells.
OBJECTIVE: The objective of this study is to investigate if bone marrow-derived cells (BMCs) regenerate vascular tissues and improve patency in tissue-engineered small-diameter (internal diameter = 3 mm) vascular grafts. SUMMARY BACKGROUND DATA: BMCs have demonstrated the ability to differentiate into endothelial-like cells and vascular smooth muscle-like cells and may offer an alternative cell source for vascular tissue engineering. Thus, we tissue-engineered small-diameter vascular grafts with BMCs and decellularized arteries. METHODS: Canine BMCs were differentiated in vitro into smooth muscle alpha-actin/smooth muscle myosin heavy-chain-positive cells and von Willebrand factor/CD31-positive cells and seeded onto decellularized canine carotid arteries (internal diameter = 3 mm). The seeded grafts were implanted in cell donor dogs. The vascular-tissue regeneration and graft patency were investigated with immunohistochemistry and angiography, respectively. RESULTS: The vascular grafts seeded with BMCs remained patent for up to 8 weeks in the canine carotid artery interposition model, whereas nonseeded grafts occluded within 2 weeks. Within 8 weeks after implantation, the vascular grafts showed regeneration of the 3 elements of artery (endothelium, media, and adventitia). BMCs labeled with a fluorescent dye prior to implantation were detected in the retrieved vascular grafts, indicating that the BMCs participated in the vascular tissue regeneration. CONCLUSIONS: Here we show that BMCs have the potential to regenerate vascular tissues and improve patency in tissue-engineered small-diameter vascular grafts. This is the first report of a small-diameter neovessel engineered with BMCs as a cell source.
Animals↗
Insulin resistance is associated with arterial stiffness in nondiabetic hypertensives independent of metabolic status.
We sought to determine whether insulin resistance (IR) is related to arterial stiffness in nondiabetic hypertensive patients, independent of metabolic status and gender. IR has been associated with increased arterial stiffness in patients with diabetes. In nondiabetic hypertensive patients, the correlation between IR and arterial stiffness has yet to be investigated. We enrolled 284 nondiabetic patients who were being treated for hypertension. At the time of enrollment, the patients underwent a baseline laboratory assessment including homeostatic model assessment (HOMA) IR index and pulse wave velocity (PWV). The HOMA IR index is used as a marker of IR, and brachial to ankle PWV (baPWV) was used as a marker of arterial stiffness. Of the 284 study subjects, 121 were classified as having metabolic syndrome. The patients with metabolic syndrome were older than the non-metabolic syndrome patients (55.4+/-10.7 vs. 52.1+/-11.6 years, p=0.013), but there was no gender difference between the two groups. The average baPWV was significantly higher in the patients with metabolic syndrome (1,506+/-235 vs. 1,435+/-211 cm/s, p=0.009). The HOMA index was independently associated with an increase in arterial stiffness (r=0.548, p<0.001) after controlling for age, systolic blood pressure (SBP), heart rate, medication and gender. The independent association of HOMA with arterial stiffness was demonstrated in subgroup analysis, regardless of the metabolic status and gender. In conclusion, increased IR was associated with arterial stiffness, independent of age, baseline SBP, gender and heart rate. This independent association of IR was demonstrated regardless of gender and metabolic status.
Adult↗
Dominant negative insulin-like growth factor-1 receptor inhibits neointimal formation through suppression of vascular smooth muscle cell migration and proliferation, and induction of apoptosis.
Blocking of the IGF-1 signaling pathway targeting the IGF-1 receptor (IGF-1R) provides a potential treatment strategy for restenosis. In this study, we have examined the effects of a dominant negative IGF-1R (IGF-1Rt) on primary rat VSMCs in vitro and on injured rat carotid artery in vivo. Ad/IGF-1Rt infection inhibited VSMC migration and proliferation, and it also induced apoptosis by inhibiting phosphorylation of Akt and phosphorylation of ERK1/2. Consistent with the anti-proliferative and apoptotic effects in vitro, the Ad/IGF-1Rt infection markedly reduced neointimal formation in carotid injury model. Ad/IGF-1Rt treated carotid arteries exhibited a suppressed proliferation index, PCNA expression, and also were stained positive for TUNEL assay. These results indicate that a dominant negative IGF-1R has the potential to reduce neointimal formation of injured rats' carotid arteries. The delivery of dominant negative IGF-1R by adenoviral or other vectors may provide a useful strategy for inhibiting restenosis after angioplasty.
Angioplasty, Balloon↗
Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome.
The SCN5A gene encodes the alpha subunit of the human cardiac voltage-gated sodium channel. Mutations in SCN5A are responsible for Brugada syndrome, an inherited cardiac disease that leads to idiopathic ventricular fibrillation (IVF) and sudden death. In this study, we screened nine individuals from a single family and 12 sporadic patients who were clinically diagnosed with Brugada syndrome. Using PCR-SSCP, DHPLC, and DNA sequencing analysis, we identified a novel single missense mutation associated with Brugada syndrome in the family and detected a C5607T polymorphism in Korean subjects. A single nucleotide substitution of G to A at nucleotide position 3934 changed the coding sense of exon 21 of the SCN5A from glycine to serine (G1262S) in segment 2 of domain III (DIII-S2). Four individuals in the family carried the identical mutation in the SCN5A gene, but none of the 12 sporadic patients did. This mutation was not found in 150 unrelated normal individuals. This finding is the first report of a novel mutation in SCN5A associated with Brugada syndrome in Koreans.
Base Sequence↗