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Yu-Lin Ko

Publications and source records attributed to Yu-Lin Ko.

14 recordsLinked to original sources
PubMed2025

Genetic Determinants of Leisure-Time Physical Activity in the Taiwanese Population: A Genome-Wide Association Study.

BACKGROUND: Physical inactivity contributes to systemic disease burden and premature mortality worldwide. Leisure-time physical activity (LTPA) improves health outcomes; however, its genetic determinants, particularly in Asian populations, remain unclear. This study aimed to identify genetic loci associated with LTPA in the Taiwanese population. METHODS: We conducted genome-wide association studies in 122,258 Taiwan Biobank participants. LTPA was assessed both as a binary trait (regular exerciser vs non-exerciser) and an ordinal trait (categorized by MET-hours per week into low, moderate, and high physical activity levels). Logistic and ordinal logistic regression models were used under an additive genetic model, adjusting for age, age 2 , sex, body mass index, smoking, and the first 10 genetic principal components. Candidate nonsynonymous mutations were further examined in 1494 whole-genome sequenced participants. RESULTS: Binary trait genome-wide association studies identified genome-wide significant (GWS) loci at ATXN2 (12q24.12), FTO (16q12.2), and NOTCH4 (6p21.32), with associations for FTO and NOTCH4 only observed in body mass index (BMI)-adjusted models. Ordinal trait analysis (<10, 10-<20, &#x2265;20 MET&#xb7;h&#xb7;wk -1 ) identified a single GWS locus at BRAP (12q24.12). Fine-mapping of 12q24.12 revealed multiple GWS single-nucleotide polymorphisms (SNPs) in strong linkage disequilibrium with lead variants; these signals largely disappeared after conditional analysis, consistent with a single underlying association. Whole-genome sequencing and linkage disequilibrium analysis identified three GWS nonsynonymous mutations, with ALDH2 rs671 emerging as the most likely causal variant. CONCLUSIONS: ATXN2-ALDH2 region on chromosome 12q24.12 was identified as a key locus for LTPA in Taiwanese individuals. These findings enhance our understanding of the genetic basis of physical activity and may inform future precision medicine and public health strategies.

Adult↗
PubMed2006

Heart rate variability characterization in daily physical activities using wavelet analysis and multilayer fuzzy activity clustering.

A portable data recorder was developed to parallel measure the electrocardiogram and body accelerations. A multilayer fuzzy clustering algorithm was proposed to classify the physical activity based on body accelerations. Discrete wavelet transform was incorporated to retrieve time-varying characteristics of heart rate variability under different physical activities. Nine healthy subjects were included to investigate activity-related heart rate variability during 24 h. The results showed that the heartbeat fluctuations in high frequencies were the greatest during lying and the smallest during standing. Moreover, very-low-frequency heartbeat fluctuations during low activity level (lying) were greater than during high activity level (nonlying).

Activities of Daily Living↗
PubMed2005

Functional polymorphisms of FGA, encoding alpha fibrinogen, are associated with susceptibility to venous thromboembolism in a Taiwanese population.

To determine the genetic risk factors for venous thromboembolism (VTE), this study examined 14 genetic variants from 10 hemostatic genes in 186 Taiwanese VTE patients and the same number of matched controls, which demonstrated FGA (encoding alpha fibrinogen) Thr312Ala polymorphism was the only variant significantly associated with VTE. Nine genetic polymorphisms on the fibrinogen cluster region of chromosome 4q28 were further studied, in which four FGA polymorphisms were found in strong linkage disequilibrium and were significantly associated with VTE by genotype and allele frequency analyses. Haplotype analysis showed significantly different FGA haplotype frequencies between VTE patients and controls with the haplotype F1, containing -1051G, -3A, 312Ala and TaqI duplication alleles, significantly associated with susceptibility to VTE (P = 0.001). Haplotype-pair analysis results also indicated a strong association of the haplotype-pair F1F1 with VTE in various VTE patient subgroups. In vitro functional analysis indicated that FGA -1051G, -3A and TaqI duplication alleles enhanced significantly the transcription level of FGA; however, control subjects with FGA genotypes containing these alleles had no elevated plasma fibrinogen levels. In conclusion, our experimental data indicated that functional genetic variants in FGA are risk factors for VTE in Taiwanese populations. Determination of FGA genotypes will likely contribute to primary prevention of this condition.

Adult↗
PubMed2005

Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms.

Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations.

Chromatography, High Pressure Liquid↗
PubMed2005

Genetic variations of apolipoprotein A5 gene is associated with the risk of coronary artery disease among Chinese in Taiwan.

Recently, a T/C polymorphism of the promoter region of the APOA5 gene at position -1131 and a G/T polymorphism at position 553 were found to be associated with increased levels of plasma triglyceride. Triglyceride plays a role in coronary artery disease (CAD), so this case-control study tested for a possible link between these two APOA5 polymorphisms, their common haplotypes and the risk of CAD. The subjects included 211 CAD patients and 677 unrelated controls. A significantly higher level of triglycerides and a lower level of high-density lipoprotein cholesterol (HDL-C) were noted for carriers with -1131C than for non-carriers (P<0.001 and 0.013, respectively) among controls. Plasma triglyceride levels were significantly higher (P=0.014) in controls with genotypes that contained the c.553T allele than in homozygotes for the G allele. Subjects homozygous for the wild-type haplotype had significantly lower triglyceride levels and higher HDL-C levels than subjects with all other haplotype pairs. The -1131C homozygous carriers and c.553T heterozygous carriers were found more frequently in 211 patients with CAD than in the 317 age/sex-matched controls (P=0.008 and 0.023, respectively) in univariate analysis. The significant association between c.553T allele carriers with CAD remained in multivariate regression analysis (OR, 1.79; CI, 1.07-3.00; P=0.028), after adjustments were made for other risk factors. Notably, haplotype analysis further verified that the APOA5 -1131C and c.553T bi-loci haplotype was significantly overpresented in CAD, as compared to the controls. These results indicate that the variants of APOA5 gene modulate plasma triglyceride and may use them to predict CAD susceptibility in Taiwanese Chinese.

Alleles↗
PubMed2004

Three-dimensional reconstruction of the rabbit atrioventricular conduction axis by combining histological, desmin, and connexin mapping data.

BACKGROUND: The 3D structure of the atrioventricular conduction axis incorporating detailed cellular and molecular composition, especially that relating to gap-junctional proteins, is still unclear, impeding mechanistic understanding of cardiac rhythmic disorders. METHODS AND RESULTS: A 3D model of the rabbit atrioventricular conduction axis was reconstructed by combining histological and immunofluorescence staining on serial sections. The exact cellular boundaries, especially those between transitional cells and atrial myocardium, were demarcated by a dense and irregular desmin-labeling pattern in conductive myocardium. The model demonstrates that the atrioventricular conduction axis is segregated into 2 connecting compartments, 1 predominantly expressing connexin45 (compact node and transitional cells) and the other predominantly coexpressing connexin43 and connexin45 (His bundle, lower nodal cells, and posterior nodal extension). The transitional zone shows unique features of spatial complexity, including a bridging bilayer structure (a deep transitional zone connecting with a superficial atrial-transitional overlay) and asymmetrical continuity (wider atrial-transitional interfaces and shorter atrial-axial distances in the hisian portion than in the ostial portion). In the latter compartment, the His bundle, lower nodal cells, and posterior nodal extension form a continual axis and longitudinal transitional-axial interface. CONCLUSIONS: Key findings of the present study are the demonstration of a distinct anatomical border between transitional and atrial cells, connection between transitional cells and both lower nodal cells and posterior nodal extension, and distinctive connexin expression patterns in different compartments of the rabbit atrioventricular conduction axis. These features, synthesized in a novel 3D model, provide a structural framework for the interpretation of nodal function.

Animals↗
PubMed2004

The interactive effects of hepatic lipase gene promoter polymorphisms with sex and obesity on high-density-lipoprotein cholesterol levels in Taiwanese-Chinese.

OBJECTIVES: Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and plays a key role in reverse cholesterol transport. The aim of the current study was to test the statistical association between two HL gene promoter polymorphisms (HL-514C/T and HL-250G/A) and lipoprotein profiles in a Taiwanese-Chinese population. METHODS: A sample population of 716 Taiwanese-Chinese individuals was analyzed. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction enzyme digestion, and agarose gel electrophoresis. RESULTS: Analysis of the data revealed that these two polymorphisms are in strong linkage disequilibrium (D/D(max)=0.97, P<0.001). A significantly lower total cholesterol/HDL-C ratio was noted for carriers with the -514T and -250A alleles compared to non-carriers (P=0.007 and 0.004, respectively). A significant trend of the association was also found on the high levels of high-density-lipoprotein cholesterol (HDL-C) among carriers with the -514T and -250A alleles as opposed to that of non-carriers (P=0.030 and 0.023, respectively). Multivariate analysis has demonstrated that the effects of HL-514C/T and HL-250G/A polymorphisms on HDL-C levels were not affected by subjects' sex, body mass index, plasma triglyceride levels and the cholesterol ester transfer protein gene TaqIB polymorphism. Subgroup analysis on each sex has revealed that the two studied polymorphisms were significantly associated with HDL-C levels among males but not significant in women. The same association between obese and non-obese men was not consistent. The P-value of the respective polymorphisms on HDL-C levels were 0.012 and 0.002 among obese men, but not significant among non-obese men. CONCLUSION: Analysis of our data revealed an independent association between the HL gene promoter polymorphisms and HDL-C levels in Taiwanese-Chinese. The data also suggests that the HL-514C/T and HL-250G/A polymorphisms interact with sex and obesity on HDL-C levels. The findings give clues for identifying high risk population in preventive medicine and clinical diagnosis. The subsequent impacts on treatment profiles and prognosis were derived from this study.

Asian People↗
PubMed2004

Highly increased cell proliferation activity in the restenotic hemodialysis vascular access after percutaneous transluminal angioplasty: implication in prevention of restenosis.

BACKGROUND: The effect of percutaneous transluminal angioplasty (PTA) in the treatment of hemodialysis vascular access stenosis is attenuated by a high restenosis rate, which results mainly from neointimal hyperplasia. Cellular proliferation is one of the most important biological mechanisms involved in neointimal hyperplasia and may be a potential target of intervention to prevent restenosis. METHODS: We investigated the activity of cellular proliferation of restenotic lesions by means of immunohistochemistry, using an antibody to the proliferating cell nuclear antigen. Specimens from 10 primary stenotic and 20 restenotic lesions of 30 Brescia-Cimino fistulae were obtained during revision. RESULTS: The proliferation index of the restenotic group was strikingly significantly greater than that of the primary stenotic group (intima, P < 0.001; media, P = 0.001). Proliferation indices of patients with diabetes in the restenotic group were significantly higher than those of patients without diabetes (intima, P = 0.028; media, P = 0.002). In the restenotic group, proliferation indices correlated negatively with the interval from PTA to restenosis (intima, r = -0.741; P < 0.001; media, r = -0.589; P = 0.006) and positively with the number of PTAs per lesion (intima, r = 0.754; P < 0.001; media, r = 0.506; P = 0.004). CONCLUSION: We show markedly high cellular proliferation activity in early restenotic lesions of arteriovenous fistulae. These findings indicate that adjunctive antiproliferative therapy is mandatory in preventing restenosis after PTA, especially in patients with diabetes.

Adolescent↗
PubMed2003

Association between a novel 11-base pair deletion mutation in the promoter region of the scavenger receptor class B type I gene and plasma HDL cholesterol levels in Taiwanese Chinese.

OBJECTIVE: Scavenger receptor class B type I (SR-BI) is a multiligand cell-surface receptor that mediates the selective uptake of lipid from HDL cholesterol (HDL-C) into cells. This study hypothesized an association between functional variants in the promoter region of SR-BI gene and HDL-C levels. METHODS AND RESULTS: We identified 2 novel mutations in the SR-BI gene promoter region by using single-strand conformation polymorphism. One mutation was an 11-bp CCCCGCCCCGT deletion mutation from positions -140 to -150 relative to the transcription start site, corresponding to an Sp1 binding site; the other was a C-->T substitution at position -142. Twenty-six of 690 unrelated subjects were heterozygous for the -140 to -150 deletion mutation, and the allele frequency in this population was 0.02. This study showed that the deletion variant prevented binding of Sp1 to this region of the SR-BI promoter and effectively reduced transcriptional activities in HepG2 cells. Notably, the -140 to -150 deletion mutation was significantly associated with increased HDL-C levels and explained approximately 0.5% of the variation in HDL-C levels in this population. CONCLUSIONS: A genetic variant at the SR-BI gene promoter region might explain a significant proportion of individual differences in HDL-C levels among Taiwanese Chinese. Our results require further replication in an independent population.

Asian People↗
PubMed2003

Giant coronary artery aneurysm mimicking a paracardiac mass.

Although either coronary artery aneurysm or coronary arterio-venous fistula may be found infrequently during coronary angiography, it is very rare to see combination of both structures. Here we present a case of coronary artery fistula combined with a large aneurysm. The aneurysm resembled a mass just beside the left heart border in the chest X-ray (CXR) film. The patient came to our hospital for chest pain. A grade 2/6 continuous murmur was noted over left upper sternal border. The mass was proved to be a coronary artery aneurysm at last by coronary angiogram after many examinations. Two coronary aterio-venous fistulae were also noted. This reminded us that coronary artery aneurysm could be one of the differential diagnoses of paracardiac mass during the interpretation of a CXR film. A high level of suspicion and a detailed physical examination combined with an adequate image studies, (such as echocardiography, computed tomography, magnetic resonance image, or coronary angiography) may provide accurate diagnosis and avoid painful, invasive examinations.

Aged↗
PubMed2002

Adriamycin-induced cardiomyocyte and endothelial cell apoptosis: in vitro and in vivo studies.

Adriamycin is a potent, broad-spectrum chemotherapeutic agent effective against solid tumors and malignant hematological disease. The major limiting factor for adriamycin is its cardiotoxicity. Thus, the objective of this study was to investigate the role of cardiomyocyte and endothelial cell apoptosis in adriamycin-induced cardiomyopathy, in vivo and in vitro. For in vivo study, intraperitoneal injections of adriamycin were administered to nine adult male Wistar rats and normal saline to six rats as control. Eight of the nine rats in the adriamycin group, but none in the control group, developed marked ascites and DNA ladders in agarose gel electrophoresis of genomic DNA extracted from the rat hearts (P<0.001). The ratio of apoptotic nuclei in the cardiomyocytes was significantly higher for the adriamycin-treated rats (162+/-149/10(6) cells) than for the controls (4.2+/-1.3/10(6) cells; P<0.01) by TUNEL assay. Increased endothelial cell apoptosis was detected in the small coronary vessels of the myocardium of the adriamycin-treated rats. Increased immuno-reactive Caspase-3 expression was also noted for both cardiomyocytes and endothelial cells of adriamycin-treated rats. In vitro adriamycin treatment for cultured neonatal rat cardiomyocytes and human umbilical vein endothelial cells, respectively, showed a dose-related increase in apoptosis as determined by flowcytometry, DNA ladder analysis, TUNEL assay and/or electron-microscope examination. A dose-related increase in the expression of Fas antigen, Bax and Caspase-3, as well as a decrease in the expression of Bcl-2, were determined for the adriamycin-treated cardiomyocytes using Northern blot analysis, reverse transcriptase polymerase chain reaction (RT-PCR) and ribonuclease protection assay. RT-PCR also revealed increased Fas antigen expression, decreased Bcl-2 expression, and no change in Bax expression for the adriamycin-treated human umbilical vein cells. Further, pretreatment with broad caspase inhibitor, but not neutralizing FasL antibody, resulted in inhibition of adriamycin-induced endothelial cell apoptosis. In conclusion, these results indicate that both adriamycin-induced cardiomyocyte and endothelial cell death can occur via apoptosis which is dose-related, and can occur both in vitro and in vivo with changes in the expression of the apoptosis-related genes. Adriamycin-induced endothelial cell apoptosis is mediated by caspase activation but is Fas/FasL signal pathway independent. Our data provides evidence that both cardiomyocyte and endothelial cell apoptosis may play an important role in adriamycin-induced cardiomyopathy.

Amino Acid Chloromethyl Ketones↗
PubMed2002

An unusual case of dual coronary artery fistulas to main pulmonary artery.

Coronary artery fistula is an anomaly in which a coronary artery directly connects to a cardiac chamber or great vessel. Its incidence is around 0.1 to 1% in the adult population. Dual coronary artery fistulas are far less common and their incidence is estimated to be around 5% in patients with this anomaly. Closure of the fistulas is indicated in patients with myocardial ischemia, large left to right shunt, congestive heart failure or other complications. Herein, we report a 64 year-old man with dual coronary artery fistulas presenting with exertional chest pain. The fistulas were initially suspected on transesophageal echocardiogram because of abnormal flow with a mosaic pattern between the left anterior descending and main pulmonary arteries. Selective coronary angiogram confirmed the diagnosis and revealed fistulous connections from the proximal left anterior descending and ostial right coronary arteries to the main pulmonary artery. The patient became symptom-free after surgical closure of the fistulas.

Coronary Disease↗
PubMed2001

Genetic variations in the cholesteryl ester transfer protein gene and high density lipoprotein cholesterol levels in Taiwanese Chinese.

This study analyzed the association of the I14A mutation, the D442G mutation, and the TaqIB polymorphism of the cholesteryl ester transfer protein (CETP) gene in 718 Chinese individuals with high-density lipoprotein cholesterol levels (HDL-C) living in Taiwan. The analysis revealed that the I14A mutation was not present in any of the 110 subjects with HDL-C levels above 60 mg/dl. By contrast, the D442G mutation was present in 48 of the 718 (6.7%) subjects tested. Significantly higher HDL-C levels were noted for bearers of the D442G mutation compared with non-bearers; however, this association was weaker for males and for subjects carrying the TaqIB1 allele. The TaqIB2 allele was also associated with higher HDL-C levels. From multivariate analysis, independent associations were demonstrated for the TaqIB2 polymorphism and the D442G mutation, and elevated HDL-C levels. For obese subjects, however, the presence of the TaqIB2 or D442G allele was not associated with increased HDL-C levels. For subjects with triglycerides at a concentration greater than 150 mg/dl, the association of both alleles with HDL-C levels was also diminished. Thus, genetic variation at the CETP gene locus may account for a significant proportion of the difference in HDL-C levels; however, it seems reasonable to suggest that the effects of the allele interact with genetic variations expressed within the sample population, and with sex, obesity, and plasma triglyceride levels.

Alleles↗