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Chia-Ti Tsai

Publications and source records attributed to Chia-Ti Tsai.

12 recordsLinked to original sources
PubMed2026

Integrative genomic and transcriptomic analysis of hypertension in a Taiwanese population.

OBJECTIVES: Hypertension is highly prevalent in Asian populations and represents a major cardiovascular risk factor. However, most genome-wide association studies (GWASs) and transcriptome-wide association studies (TWASs) have focused primarily on Caucasian cohorts. This study aimed to identify genetic loci and gene expression signatures associated with hypertension in an Asian population. METHODS: We analyzed 10 739 hypertensive patients and 49 668 controls from the Taiwan Biobank, testing 4 512 191 genome-wide single nucleotide polymorphisms (SNPs). Integrated GWAS, TWAS, and expression quantitative trait locus (eQTL) analyses were conducted to characterize genetic risk. Additionally, a polygenic risk score (PRS) was constructed using a split-sample design to evaluate genetic risk stratification. RESULTS: We identified 14 loci significantly associated with hypertension, including a novel locus at 5p13.1. eQTL analysis linked this locus to DAB2 expression in whole blood. TWAS detected 55 hypertension-associated genes, with 20 (36%) overlapping GWAS loci. Several novel genes outside GWAS loci, including FBXL15, KCNIP2, and CRIP3, were highly significant and implicated in vascular biology and hypertension mechanisms. PRS analysis effectively differentiated hypertension risk, with individuals in the top 10% showing a > 3.5-fold increased risk compared to the bottom 10%. CONCLUSIONS: Our findings provide new insights into the genetic and transcriptomic landscape of hypertension in Asians. The identification of novel loci and genes advances understanding of disease biology and may guide precision medicine approaches for risk prediction and therapeutic development.

Female↗
PubMed2006

Renin-angiotensin system gene polymorphisms and coronary artery disease in a large angiographic cohort: detection of high order gene-gene interaction.

There have been many reports regarding the association between renin-angiotensin system (RAS) gene polymorphisms and coronary artery disease (CAD) or acute myocardial infarction (AMI), but the results are inconsistent. In the present study, we used several new approaches with multilocus data to reappraise this issue in a large and relatively homogeneous Taiwanese population. A total of 1254 consecutive patients who underwent cardiac catheterization (735 with documented coronary artery disease and 519 without) between 1996 and 2003 were recruited. Angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen gene; and A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In single-locus analyses, no locus was associated with CAD, history of AMI and three-vessel CAD, either with or without adjustment for conventional CAD risk factors. For multilocus analyses, we recreated a balanced population, with the controls individually matched to the cases regarding the conventional CAD risk factors. We found that the angiotensinogen gene haplotype profile was significantly different between the cases and controls (chi2=31.6, P=0.030) in haplotype analyses. Furthermore, significant three-locus (G-217A, M235T and I/D) gene-gene interactions were detected by multifactor-dimensionality reduction method (highest cross-validation consistency 10.0, lowest prediction error 40.56%, P=0.017) and many even higher order gene-gene interactions by multilocus genotype disequilibrium tests (16 genotype disequilibria exclusively found in the controls, all of which included at least two genes among AGT, ACE and AT1R genes). Our study is the first to demonstrate epistatic, high-order, gene-gene interactions between RAS gene polymorphisms and CAD. These results are compatible with the concept of multilocus and multi-gene effects in complex diseases that would be missed with conventional approaches.

Aged↗
PubMed2006

The association of human connexin 40 genetic polymorphisms with atrial fibrillation.

BACKGROUND: There is evidence showing that genetic factors contribute to the pathogenesis of atrial fibrillation (Af). We investigated the association between Af and polymorphisms of the connexin 40 (Cx40) gene, which is important in the electrical coupling between atrial myocytes. METHODS: We performed an association study between two Cx40 single nucleotide polymorphisms (SNPs) (Cx40 -44 and +71 allele) and Af. We enrolled 173 patients with Af, and the control group consisted of 232 patients without Af. The luciferase assay was performed to evaluate the promoter activities of different Cx40 haplotypes in cultured atrial myocytes. RESULTS: We found that the two SNPs were both significantly associated with Af. In pairwise linkage disequilibrium analysis, the two SNPs were completely linked (Cx40 -44G always associated with Cx40 +71A; Cx40 -44A associated with Cx40 +71G, P<0.001). In haplotype analysis, we demonstrated that the frequency of Cx40 (-44A,+71G) was significantly higher in the Af group than that in the control group (P<0.006, odds ratio=1.514, 95% confidence interval 1.13-2.04). We also performed genotype analysis using several genetic models, finding that the recessive model showed the lowest P value (P<0.004) and the largest odds ratio (2.53, 95% confidence interval 1.23-5.19). In promoter activity studies using luciferase as the reporter, Cx40 (-44A,+71G) had significantly lower promoter activity than that of the Cx40 (-44G,+71A) in atrial myocytes. CONCLUSIONS: The two SNPs in the promoter region of the Cx40 gene were significantly associated with Af. The Cx40 (-44A +71G) haplotype was associated with a higher risk for Af. This haplotype also had significantly lower promoter activity in atrial myocytes.

Aged↗
PubMed2006

A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility.

Detecting, characterizing, and interpreting gene-gene interactions or epistasis in studies of human disease susceptibility is both a mathematical and a computational challenge. To address this problem, we have previously developed a multifactor dimensionality reduction (MDR) method for collapsing high-dimensional genetic data into a single dimension (i.e. constructive induction) thus permitting interactions to be detected in relatively small sample sizes. In this paper, we describe a comprehensive and flexible framework for detecting and interpreting gene-gene interactions that utilizes advances in information theory for selecting interesting single-nucleotide polymorphisms (SNPs), MDR for constructive induction, machine learning methods for classification, and finally graphical models for interpretation. We illustrate the usefulness of this strategy using artificial datasets simulated from several different two-locus and three-locus epistasis models. We show that the accuracy, sensitivity, specificity, and precision of a naïve Bayes classifier are significantly improved when SNPs are selected based on their information gain (i.e. class entropy removed) and reduced to a single attribute using MDR. We then apply this strategy to detecting, characterizing, and interpreting epistatic models in a genetic study (n = 500) of atrial fibrillation and show that both classification and model interpretation are significantly improved.

Atrial Fibrillation↗
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

Successful radiofrequency catheter ablation of idiopathic ventricular fibrillation presented as recurrent syncope and diagnosed by an implanted loop recorder.

As a palliative therapy, an implantable cardioverter-defibrillator (ICD) could not prevent the occurrence of ventricular tachycardia or fibrillation (VT, VF), but only suppress it by overdrive pacing or direct current shocks. Recurrent VT or VF followed by frequent ICD shocks might thus put patients in a painful disaster. We presented a case of recurrent syncope diagnosed as recurrent VF by an implanted loop recorder (ILR). The VF was eliminated by radiofrequency catheter ablation (RFCA) of triggering ventricular premature complexes (VPCs).

Adult↗
PubMed2004

Renin-angiotensin system gene polymorphisms and atrial fibrillation.

BACKGROUND: The activated local atrial renin-angiotensin system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation (AF). We hypothesized that RAS genes might be among the susceptibility genes of nonfamilial structural AF and conducted a genetic case-control study to demonstrate this. METHODS AND RESULTS: A total of 250 patients with documented nonfamilial structural AF and 250 controls were selected. The controls were matched to cases on a 1-to-1 basis with regard to age, gender, presence of left ventricular dysfunction, and presence of significant valvular heart disease. The ACE gene insertion/deletion polymorphism, the T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen gene, and the A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In multilocus haplotype analysis, the angiotensinogen gene haplotype profile was significantly different between cases and controls (chi2=62.5, P=0.0002). In single-locus analysis, M235T, G-6A, and G-217A were significantly associated with AF. Frequencies of the M235, G-6, and G-217 alleles were significantly higher in cases than in controls (P=0.000, 0.005, and 0.002, respectively). The odds ratios for AF were 2.5 (95% CI 1.7 to 3.3) with M235/M235 plus M235/T235 genotype, 3.3 (95% CI 1.3 to 10.0) with G-6/G-6 genotype, and 2.0 (95% CI 1.3 to 2.5) with G-217/G-217 genotype. Furthermore, significant gene-gene interactions were detected by the multifactor-dimensionality reduction method and multilocus linkage disequilibrium tests. CONCLUSIONS: This study demonstrates the association of RAS gene polymorphisms with nonfamilial structural AF and may provide the rationale for clinical trials to investigate the use of ACE inhibitor or angiotensin II antagonist in the treatment of structural AF.

Aged↗
PubMed2003

Distinct clinical features in the recipients of the implantable cardioverter defibrillator in Taiwan: a multicenter registry study.

Little information about the ICD is available from the Asian Pacific region. The purpose of this study was to characterize the clinical features in ICD patients in Taiwan and to compare these features with those in patients in the Western populations, mainly the Canadian Implantable Defibrillator Study (CIDS), the Antiarrhythmics versus Implantable Defibrillator (AVID) trial, and the Cardiac Arrest Study Hamburg (CASH) trial. From February 1995 to October 2001, 101 ICDs were implanted in 92 patients (78 [84%] men) in 12 hospitals. Clinical presentations included sudden cardiac death due to VF/VT in 35 (38%) patients, syncopal VT in 25 (27%), drug refractory nonsyncopal VT in 27 (29%), and unexplained syncope with inducible sustained VT/VF in 5 (6%). The mean age was significantly younger than that in CIDS or AVID (59 +/- 16 vs 63 +/- 9 years in CIDS, P = 0.02; vs 65 +/- 11 years in AVID, P < 0.001), but was comparable to that in CASH (59 +/- 16 vs 58 +/- 11 years in CASH, P = 0.75). The mean LVEF was significantly higher than that in CIDS or AVID (48 +/- 19% vs 34 +/- 15% in CIDS, P < 0.001; vs 32 +/- 13% in AVID, P < 0.001), but was comparable to that in CASH (48 +/- 19 vs 46 +/- 19% in CIDS, P = 0.83). The ICD patients in the current study also showed a higher incidence of normal heart (23 vs 4% in CIDS, P < 0.001; vs 3% in AVID, P < 0.001; vs 9% in CASH, P < 0.001) and cardiomyopathy (41% vs 10% in CIDS, P < 0.001; vs 15% in AVID, P < 0.001; vs 11% in CASH, P < 0.001), but a lower incidence of coronary artery disease (29% vs 83% in CIDS, P < 0.001; vs 82% in AVID, P < 0.001; vs 73% in CASH, P < 0.001). During a mean follow-up of 28 +/- 24 months, 13 (14%) patients died. Older age was the only factor associated with poorer survival after ICD implantation. Forty-seven (51%) patients received appropriate ICD discharges during follow-up. History of prior myocardial infarction was the only factor associated with an earlier first appropriate ICD discharge and LVEF < 0.35 the only factor associated with subsequent poorer survival after the first ICD discharge. In conclusion, this study demonstrated many distinct clinical features in our ICD population that were different from those in the Western populations.

Aged↗
PubMed2003

Characteristics of Chinese patients with symptomatic Brugada syndrome in Taiwan.

Since 1992, the Brugada syndrome has been increasingly recognized worldwide, although its incidence and distribution remain unclear. In Asia, several cases have been reported in Japan, Thailand, Singapore, and Vietnam. However, little information is available from the Chinese population. Since June 1997, we have identified 10 patients with the diagnosis of the Brugada syndrome from six hospitals in Taiwan. All patients were male with the mean age of 46 +/- 7 years (range 36-61). They all had a normal chemistry profile, coronary angiography and echocardiography. Clinical presentations varied from seizure and syncope to sudden cardiac death. MRI and ultrafast CT of the heart did not show any abnormalities. Sustained ventricular tachycardia/ventricular fibrillation (VF) was induced in 7 of 8 patients who underwent an electrophysiologic study. The pharmacological provocation test was positive in 4 of 5 patients. One of the 4 patients who had a genetic study showed SCN5A gene mutation. An implantable cardioverter defibrillator (ICD) was implanted in 8 patients. During a mean follow-up of 29 +/- 17 months (range 2-54), 3 of 8 patients who had an ICD received appropriate ICD discharges after implantation. These 3 patients who were subsequently treated with antiarrhythmic agents have had no further recurrent ICD discharges. Two patients who refused ICD implantation are alive and well without taking antiarrhythmic agents. Our study showed that the clinical characteristics of our patients are similar to those described in the literature and that ICD is an effective treatment modality for patients with recurrent VF. However, antiarrhythmic agents may be beneficial for suppressing arrhythmia recurrences in selected patients.

Adult↗
PubMed2003

Angiotensinogen gene haplotype and hypertension: interaction with ACE gene I allele.

There are many reports demonstrating the association of renin-angiotensin system gene polymorphisms with hypertension in different populations. In the present study, we used haplotype analyses of the angiotensinogen gene with a new permutation-based hypothesis testing method to determine the association between multilocus angiotensinogen gene polymorphisms and hypertension in a relatively homogeneous Taiwanese population. We also genotyped angiotensin-converting enzyme gene insertion/deletion polymorphism and angiotensin II type 1-receptor gene A1166C polymorphism to detect epistatic gene-gene interactions. There were 408 patients with hypertension (hypertensives) and 286 controls. The angiotensinogen gene haplotype frequencies were significantly different between hypertensives and controls, and this finding was only present in subjects with angiotensin-converting enzyme gene II genotypes when the analysis was stratified by genotype of this polymorphism. In addition, the angiotensinogen gene haplotype structure of hypertensives was more heterogeneous than that of controls. Our results showed that angiotensinogen gene haplotypes were associated with hypertension and might act synergistically with I allele of the angiotensin-converting enzyme gene.

Alleles↗
PubMed2002

The 27-bp tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene is not associated with coronary artery disease in a hospital-based Taiwanese population.

We studied whether the 27 base pair (bp) tandem repeat polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene was associated with coronary artery disease (CAD) in a hospital-based Taiwanese population. We included 219 consecutive patients who underwent coronary angiography at our institution. Two alleles, containing 4 (eNOS4a) and 5 repeats (eNOS4b), were identified after polymerase chain reaction amplifying intron 4 of the eNOS gene. The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 77.9, 21.5 and 0.6% in CAD subjects, and 80, 20 and 0% in control subjects (Fisher's exact test, p = 0.90), respectively. The odds ratio (OR) for CAD in patients with at least one eNOSa allele was 1.2 (0.5-2.9) after adjustment for classical CAD risk factors. The eNOS4a allele was not associated with the severity of CAD (Fisher's exact test, p = 0.90) and the occurrence of acute myocardial infarction (AMI) or unstable angina (adjusted OR 0.6, 0.3-1.6) in patients with CAD. In conclusion, the 27-bp repeat polymorphism of the eNOS gene was not associated with CAD and the occurrence of AMI or unstable angina in a hospital-based Taiwanese population.

Aged↗