[Show abstract][Hide abstract] ABSTRACT: Background/purpose:
Recent studies suggest that hyperuricemia is a potential risk factor for cardiovascular disease (CVD). Hyperuricemia is highly heritable and is associated with sex and body weight. Previous genome-wide association studies have found that the ABCG2 single nucleotide polymorphism (SNP) rs2231142 is an important genetic factor for increased uric acid (UA) levels, and the degree of association between rs2231142 and hyperuricemia is affected by both sex and ethnicity. This investigation aimed to analyze the association between ABCG2 polymorphisms and UA levels, as well as their interactions with sex and obesity in Taiwanese.
Two genetic polymorphisms around the ABCG2 gene were genotyped in 459 patients.
After adjusting for clinical covariates, the rs2231142 SNP was found significantly associated with UA levels using a dominant inheritance model. Patients carrying the rs2231142-A allele had a higher frequency of hyperuricemia than those with the rs2231142-CC allele. Subgroup analysis revealed an association of rs2231142 with UA levels in male or obese patients, and there was no association in nonobese female patients.
The rs2231142 SNP is associated with serum UA levels and hyperuricemia in Taiwanese patients and it occurs predominantly in male or obese patients. Hyperuricemia might be controlled differently by sex and obesity.
Preview · Article · Jan 2016 · Journal of the Formosan Medical Association
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Heart-rate corrected QT (QTc) interval predicts cardiovascular mortality or all-cause mortality in the general population. Little is known about the best cut-off value of QTc interval for predicting clinical events in patients with ST-elevation myocardial infarction (STEMI).
We enrolled 264 patients with STEMI who received measurement of QTc intervals at ER (QTc-ER), on day 2 (QTc-D2), and on day 3 (QTc-D3) of hospitalization. Clinical events, including all-cause death and readmission for heart failure, were followed for 2 years.
Prolonged QTc-ER, but not QTc-D2 or QTc-D3, well predicted clinical events with the best cut-off value of 445 ms. Patient with QTc-ER > 445 ms had lower left ventricular ejection fraction at baseline and at 6 months. Kaplan-Meier survival curves showed that the combination of QTc-ER > 445 ms and N-terminal pro-brain natriuretic peptide (NT-pro BNP) > 936 pg/mL was a strong predictor of clinical events (p<0.001). In multivariable Cox regression analysis, the independent predictors of death and heart failure were QTc-ER (p<0.001), log NT-proBNP (p<0.001), diabetes mellitus (p<0.001), history of stroke (p=0.001), and left ventricular end diastolic volume index (p<0.001).
QTc-ER > 445 ms independently predicts clinical events in STEMI, providing incremental prognostic value to established clinical predictors and NT-proBNP.
No preview · Article · Dec 2015 · International journal of medical sciences
[Show abstract][Hide abstract] ABSTRACT: CDH13
gene variants with lower adiponectin levels are paradoxically associated with a more favorable metabolic profile. We investigated the statistical association between
locus variants and adiponectin levels by examining 12 circulating inflammation marker levels and adiposity status in 530 Han Chinese people in Taiwan. After adjustments for clinical covariates, adiponectin levels were positively associated with soluble vascular cell adhesion molecule-1 (sVCAM1) levels and negatively associated with adiposity status and levels of C-reactive protein (CRP), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM1). In addition, minor alleles of the
rs12051272 polymorphism were found to have lower adiponectin levels and higher CRP, sE-selectin, sICAM1, and sVCAM1 levels as well as higher body mass indices and waist circumferences in participants (all
). In a subgroup analysis stratified by sex, significant associations between
genotypes and sE-selectin levels occurred only in men (
locus variants and adiponectin levels are associated with circulating levels of cellular adhesion molecules and adiposity status in a differential manner that interacts with sex. These results provide further evidence for the crucial role of adiponectin levels and
gene variants in immune-mediated and inflammatory diseases.
Preview · Article · Nov 2015 · Mediators of Inflammation
[Show abstract][Hide abstract] ABSTRACT: Background:
Clinical outcomes of the drug-coated balloon (DCB) procedure in high-risk patients with femoropopliteal (FP) disease have not been investigated sufficiently.
This retrospective, single-center study analyzed 87 patients (39% dialysis) and 97 affected legs (64% critical limb ischemia [CLI]) that underwent DCB for symptomatic FP disease from March 2013 to September 2014. Risk stratification was based on FeDCLIP (female, diabetes, dialysis, CLI, lesion length >150 mm and poor runoff) score. The DCB outcomes among the different risk groups were compared and factors predicting restenosis were analyzed during follow-up.
Most of study participants (84%) were moderate to high-risk patients. The procedural success rate was 100% and the 30-day major adverse vascular event rate was 2.1%. The mean lesion length was 178 ± 106 mm and the mean follow-up time was 428 ± 145 (range 50-782) days. The binary restenosis-free and clinically driven target lesion revascularization (CD-TLR)-free rates at 12 months were 77.5% and 84.3%, respectively, for all participants. No significant differences were observed in 1-year binary restenosis and CD-TLR rates in the low-, moderate-, and high-risk groups (60%, 84%, and 73%: p = 0.396; 78%, 89%, and 80%: p = 0.635, respectively). In multivariate analysis, lesion length >150 mm (Hazard ratio [HR]: 8.00, 95% confidence interval (CI) 1.12 to 55.6, p = 0.038) and Rutherford class 6 (HR: 7.09, 95% CI, 1.15 to 43.5, p = 0.034) were identified as independent predictors of binary restenosis.
Despite general comorbidities and advanced limb ischemia, 1-year outcomes of DCB in high-risk patients with FP disease were effective. The DCB procedure holds promise to improve vessel patency; however, lesion length >150 mm and major tissue loss were independent predictors for binary restenosis after the treatment.
[Show abstract][Hide abstract] ABSTRACT: The TBX5 gene, a member of the T-box family, is associated with congenital heart disease, electrocardiographic parameters, and development of atrial fibrillation in the general population. This study aimed to elucidate the role of TBX5 gene polymorphisms in metabolic and inflammatory profiles possibly linked to TBX5-related pathologies.
No preview · Article · Nov 2015 · Tzu Chi Medical Journal
[Show abstract][Hide abstract] ABSTRACT: Objective:
Previous genome-wide association studies have indicated an association between CDH13 genotypes and adiponectin levels. In this study, we used mediation analysis to assess the statistical association between CDH13 locus variants and adiponectin levels, metabolic syndrome, and related metabolic phenotypes.
Methods and results:
A sample population of 530 Taiwanese participants was enrolled. Four CDH13 gene variants in the promoter and intron 1 regions were genotyped. After adjustment for clinical covariates, the CDH13 genotypes/haplotypes exhibited an association with the adiponectin levels (lowest P = 1.95 × 10-11 for rs4783244 and lowest P = 3.78 × 10-13 for haplotype ATTT). Significant correlations were observed between the adiponectin levels and the various metabolic syndrome-related phenotypes (all P ≤ 0.005). After further adjustment for the adiponectin levels, participants with a minor allele of rs12051272 revealed a considerable association with a more favorable metabolic profile, including higher insulin sensitivity, high-density lipoprotein cholesterol levels, lower diastolic blood pressure, circulating levels of fasting plasma glucose, and triglycerides, and as a lower risk of metabolic syndrome (all P < 0.05). The mediation analysis further revealed a suppression effect of the adiponectin levels on the association between CDH13 genotypes and metabolic syndrome and its related phenotypes (Sobel test; all P < 0.001).
The genetic polymorphisms at the CDH13 locus independently affect the adiponectin levels, whereas the adiponectin levels exhibit a suppressive effect on the association between CDH13 locus variants and various metabolic phenotypes and metabolic syndrome. In addition, these results provide further evidence of the association between the CDH13 gene variants and the risks of metabolic syndrome and atherosclerotic cardiovascular disease.
[Show abstract][Hide abstract] ABSTRACT: Body weight regulation is influenced neuronally via the hypothalamus, which strongly expresses TRPV4. TRPV4 deficiency in mice confers resistance against diet-induced obesity. We investigated the association between TRPV4 gene variants and body mass index (BMI) in Taiwanese subjects. A sample population of 617 Taiwanese subjects was enrolled, and ten TRPV4 gene polymorphisms were selected and genotyped. After adjusting for clinical covariates, significant associations were observed between three studied polymorphisms and BMI using a dominant model (P = 4.83 × 10−4, P = 1.17 × 10−4, and P = 3.37 × 10−4 for rs3742037, rs10735104, and rs3742035, respectively). Obesity as defined according to both the Asian and National Institutes of Health (NIH) criteria was significantly associated with rs10735104 (P = 0.003 and P = 0.037, respectively) in a dominant model. Genotypes at the TRPV4 locus independently affect BMI and obesity status in Taiwanese subjects. This association may broaden our understanding of the role of neuronal influence on body weight regulation. The regulation of TRPV4 channels in skeletal muscle and adipose tissue could also be a new therapeutic target for preventing the development of obesity.
No preview · Article · Feb 2015 · Molecular Genetics and Genomics
[Show abstract][Hide abstract] ABSTRACT: YKL-40, a pleotropic cytokine, is emerging as a risk factor and a prognostic predictor of atherosclerotic cardiovascular disease. We attempted to elucidate the genetic, clinical and biochemical correlates of circulating YKL-40 level and, by combining it with CHI3L1 gene variants, with the risk and long-term mortality of peripheral artery disease (PAD). Plasma YKL-40 concentrations were measured in 612 Taiwanese individuals who had no clinically overt systemic disease. Clinical parameters, CHI3L1 gene promoter variants and 18 biomarker levels were analyzed. Eighty-six PAD patients were further enrolled for analysis. Significant associations were found between CHI3L1 genotypes/haplotypes and YKL-40 levels for the health examination subjects (smallest p = 8.36 × 10-7 for rs4950928 and smallest p = 1.72 × 10-10 for haplotype TGG) and also for PAD patients. For the health examination subjects, circulating YKL-40 level, but not CHI3L1 gene variants, were positively associated with age, smoking, and circulating levels of triglyceride, lipocalin 2 and multiple inflammatory biomarkers and negatively associated with low-density-lipoprotein cholesterol levels. Circulating YKL-40 level is also significantly associated with the risk of PAD (p = 3.3 × 10-23). Circulating YKL40 level, but not CHI3L1 gene promoter variants, is associated with the risk of PAD in Taiwanese. The association of YKL-40 levels with multiple quantitative traits relating to the risk of PAD may provide a molecular basis linking YKL-40 to atherosclerotic cardiovascular disease.
Full-text · Article · Dec 2014 · International Journal of Molecular Sciences
[Show abstract][Hide abstract] ABSTRACT: Growth-differentiation factor (GDF)-15 is a strong predictor of cardiovascular events in patients with ST-elevation myocardial infarction (STEMI). However, the effects of GDF-15 on left ventricular (LV) remodeling have not been clearly elucidated. The aim of this study is to investigate whether GDF-15 will be of benefit in predicting LV remodeling, heart failure and death in patients with STEMI.
The authors enrolled 216 patients with STEMI who received measurement of GDF-15 level on day 2 of hospitalization. Echocardiographic studies were performed at baseline and were repeated 6 months later. Clinical events, including all-cause death and readmission for heart failure, were followed up for a maximum of 3 years.
Patients with GDF-15 levels above the median had lower LV ejection fraction at baseline (43.9% versus 48.0%, P = 0.041) and at 6 months (51.5% versus 56.9%, P = 0.025). In univariable regression model, log-transformed GDF-15 level was not a predictor of increase in LV end-diastolic volume index at 6 months (P = 0.767). Kaplan-Meier survival curves showed that the combination of high GDF-15 and high N-terminal pro-B-type natriuretic peptide was a strong predictor of death and heart failure (P < 0.001). In multivariable Cox regression model, the independent predictors of death and heart failure were age, GDF-15 level and diabetes mellitus.
High GDF-15 level is a strong predictor of death and heart failure in patients with STEMI. Although patients with higher GDF-15 levels tend to have lower LV ejection fraction, they have similar degree of the increase in LV end-diastolic volume index at 6 months.
Full-text · Article · Feb 2014 · The American Journal of the Medical Sciences
[Show abstract][Hide abstract] ABSTRACT: Background:
To compare the clinical outcomes between excimer laser-assisted angioplasty (ELA) with spot stent (group A) and primary stenting (group B) in intermediate to long femoropopliteal disease.
Outcomes of 105 patients totaling 119 legs treated with two different strategies were analyzed retrospectively in a prospectively maintained database.
Baseline characteristics were similar in both groups. Better angiographic results and lesser increase of serum C-reactive protein levels (0.60 ± 0.72 versus 2.98 ± 0.97 mg/dL, P < 0.001) after the intervention were obtained in Group B. Group A had inferior 1-year outcomes due to higher rate of binary restenosis (67% versus 32%, P = 0.001) and lower rate of primary patency (40% versus 58%, P = 0.039). Rates of amputation-free survival, target vessel revascularization, assisted primary patency, and stent fracture at 24 months were similar in both groups (80% versus 82%, P = 0.979, 65% versus 45%, P = 0.11, 78% versus 80%, P = 0.75 and 6.3% versus 6.8%, P = 0.71, resp.).
Greater vascular inflammation after ELA with spot stent resulted in earlier restenosis and inferior 1-year clinical outcomes than primary stenting. This benefit was lost in the primary stenting group at 2 years due to late catch-up restenosis. Active surveillance with prompt intervention was required to maintain the vessel patency.
Full-text · Article · Dec 2013 · The Scientific World Journal
[Show abstract][Hide abstract] ABSTRACT: Objective:
Previous investigations have revealed an association between the ABO locus/blood group and total cholesterol and inflammatory biomarker levels. We aimed to test the statistical association of ABO locus variants with lipid profiles and levels of thirteen inflammatory markers in a Taiwanese population.
Methods and results:
A sample population of 617 Taiwanese subjects was enrolled. Five ABO gene region polymorphisms were selected and genotyped. After adjusting for clinical covariates and inflammatory marker levels, the genetic-inferred ABO blood group genotypes were associated with sE-selectin level (P = 3.5 × 10(-36)). Significantly higher total and low-density lipoprotein cholesterol (LDL-C) levels were noted in individuals with blood group A (P = 7.2 × 10(-4) and P = 7.3 × 10(-4), respectively). Interestingly, after adjusting for sE-selectin level, significantly lower high-density lipoprotein cholesterol (HDL-C) level as well as higher triglyceride (TG) level and ratio of triglyceride to HDL-C (TG/HDL-C ratio) were noted in individuals with blood group A comparing to non-A individuals (P = 0.009, P = 0.004 and P = 0.001, respectively); these associations were also observed in the group A male subjects (P = 0.027, P = 0.001, and P = 0.002, respectively). Mediation analysis further revealed a suppression effect of sE-selectin level on the association between genetic-inferred ABO blood group genotypes and TG/HDL-C ratio in total participants (P = 1.18 × 10(-6)) and in males (P = 5.99 × 10(-5)).
Genetic variants at the ABO locus independently affect sE-selectin level in Taiwanese subjects, while the association of ABO locus variants with TG/HDL-C ratio is suppressed by sE-selectin level in Taiwanese males. These results provided further evidence for the mechanism in the association of ABO blood groups with atherosclerotic cardiovascular diseases.
[Show abstract][Hide abstract] ABSTRACT: MMP1 is implicated in the pathogenesis of atherothrombotic cardiovascular disease. We aimed to elucidate genetic determinants of inflammatory marker levels, including circulating MMP1, in Taiwanese, and their association with obesity.
Five genetic polymorphisms around matrix metalloproteinase genes on chromosome 11q21-22 region were genotyped in 519 subjects.
After adjusting for clinical covariates, two polymorphisms were significantly associated with MMP1 levels, rs1799750 and rs495366, using an additive inheritance model (P = 1.5x10-4 and P = 2.57x10-5, respectively). Using dominant model, minor alleles of rs1799750 and rs495366 were associated with higher MMP1 levels (P = 1.3x10-4 and P = 1.95x10-5, respectively). In haplotype analysis, two haplotypes inferred from five SNPs (A2GATA and A1GATG) were associated with MMP1 levels (P = 5x10-4 and P = 8.47x10-5, respectively). Subgroup and interaction analysis revealed an association of rs1799750 and rs495366 with MMP1 levels only in non-obese subjects (P = 6.66x10-6 and P = 4.38x10-5, respectively, and interaction P = 0.008 for rs1799750). Haplotype interaction analysis also showed significant interaction for haplotype A1GATG (interaction P = 0.003).
Genotypes/haplotypes around MMP1 locus are associated with MMP1 levels in Taiwanese. Further, since genotypes/haplotypes near MMP1 locus interact with obesity to set MMP1 levels, genetic determinants for MMP1 level may be different between obese and non-obese individuals.
Full-text · Article · Mar 2013 · BMC Medical Genetics
[Show abstract][Hide abstract] ABSTRACT: Background:
The frequency and clinical correlates of global right ventricular (RV) dysfunction in patients treated with primary percutaneous coronary intervention for a first acute ST-elevation myocardial infarction (STEMI) without a coexisting RV infarction is not well known.
Materials and methods:
One hundred seven consecutive patients underwent conventional echocardiography and pulsed-wave tissue Doppler imaging (TDI) within 72 hours after a successful primary percutaneous coronary intervention to assess their RV function. Global RV function was quantified with the RV myocardial performance index (MPI) by pulsed-wave TDI. An abnormal TDI-derived RV MPI was defined as greater than the upper reference limit of 0.55.
Global RV dysfunction was present in 18 (17%) of the 107 patients enrolled. The patients with global RV dysfunction had significantly higher glucose levels on admission (216 ± 102 vs 163 ± 86 mg/dL; P = 0.027), higher peak creatine kinase (4027 ± 2171 vs 2660 ± 1980 IU/L; P = 0.014), and more frequently had anterior infarcts (89% vs 58%; P = 0.016) than those without RV dysfunction. Patients with global RV dysfunction also had a significantly lower left ventricular (LV) ejection fraction (45.1 ± 10.8% vs 51.1 ± 9.7%; P = 0.021), a higher global wall motion score index (1.9 ± 0.3 vs 1.7 ± 0.4; P = 0.007), and greater LV MPI (0.65 ± 0.19 vs 0.47 ± 0.11; P = 0.001) than patients without. With the use of multivariate regression analysis, TDI-derived LV MPI (odds ratio [OR], 3.40; 95% confidence interval [CI], 1.20-9.67; P = 0.022), the ratio of transmitral peak early (E) to late diastolic filling (A) velocities (E/A ratio) (OR, 0.41; 95% CI, 0.18-0.92; P = 0.031), and admission plasma glucose level (OR, 1.01; 95% CI, 1.0-1.02; P = 0.039) were independently associated with the presence of global RV dysfunction.
In patients with a first acute STEMI without an associated RV infarction, depressed global LV function reflected by increased TDI-derived LV MPI, a lower mitral E/A ratio, and a higher glucose level on admission are independent correlates of early global RV dysfunction. Routine assessment of global RV function should be implemented in patients with STEMI with these characteristics.
No preview · Article · Feb 2013 · Journal of Investigative Medicine
[Show abstract][Hide abstract] ABSTRACT: Background
E-selectin is implicated in various inflammatory processes and related disorders. We aimed to investigate the role of SELE-gene genotypes/haplotypes on plasma levels of MMP9 and sE-selectin in Taiwanese individuals.
Five hundred twenty individuals were enrolled. Seven tagging SELE single nucleotide polymorphisms were analyzed.
SELE genotypes were found associated with MMP9 and sE-selectin levels. Multivariate analysis identified that the most significant genetic polymorphism (rs5368 genotype) was independently associated with MMP9 levels (P < 0.001). One haplotype (GGAGAGT) was marginally associated with MMP9 levels (P = 0.0490). One SELE SNP, (rs3917406, P = 0.031) was associated with sE-selectin levels after adjusting for MMP9 and sICAM1 levels. Subgroup and interaction analysis revealed association of SELE SNP rs10800469 with sE-selectin levels only in the highest quartile of MMP9 level (P = 0.002, interaction P = 0.023). Haplotype analysis showed one haplotype (AAAAAGC) borderline associated with sE-selectin level (P = 0.0511).
SELE genotypes/haplotypes are independently associated with MMP9 and E-selectin levels in Taiwanese individuals. The associations of SELE genotypes/haplotypes with sE-selectin levels are affected by MMP9 levels.
Full-text · Article · Nov 2012 · BMC Medical Genetics
[Show abstract][Hide abstract] ABSTRACT: Background: There have been conflicting reports of the association between the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene, and the risk of venous thromboembolism (VTE). We sought to investigate the association between ACE I/D polymorphism, and the risk of VTE in a Chinese population living in Taiwan. Methods: 176 patients with VTE and 321 age and sex-matched controls were analyzed for the ACE I/D polymorphism by polymerase chain reaction. Results: The genotype distribution of the ACE I/D polymorphism was not statistically different between the VTE affected subjects and the group of unaffected subjects (p = 0.057). Notably, the frequency of ACE D allele in patients with VTE were significantly lower than that in the control group (28% vs. 35%, p = 0.018). After adjusting for age, gender, smoking, hypertension, diabetes and body mass index (BMI), the ACE D allele carriers remained significantly associated with a decreased risk of VTE. Further meta-analysis by pooling data from 15 studies revealed that neither the DD, nor the II genotype, was found to be associated with VTE (pooled unadjusted odds ratio were 1.167, 95% confidence intervals, 0.927-1.470, p = 0.189 for DD, and 1.085, 95% confidence intervals, 0.875-1.345 p = 0.460 for II). Conclusion: Our results suggest that the presence of the D allele may confer protection against the development of VTE in an ethnically Chinese population in Taiwan. Further meta-analysis did not support a relationship between the ACE I/D polymorphism and the risk of VTE.
Full-text · Article · Dec 2011 · Acta Cardiologica Sinica
[Show abstract][Hide abstract] ABSTRACT: Background: Both albuminuria and oxidative stress predict future cardiovascular disease and atherosclerosis. Mounting evidence indicates that oxidative stress plays an important role in the development of albuminuria in diabetes and hypertensive patients. We aimed to test oxidative stress as a potential early risk factor of microalbuminuria by examining the statistical associations between albuminuria and oxidative stress in a Taiwanese population. Methods: A sample population of 469 Taiwanese subjects (241 men and 228 women) was enrolled. Urinary albumin concentrations were presented as urinary albumin-to-creatinine ratio (ACR). Oxidative stress was estimated by measuring urinary 8-hydroxydeoxyguanosine (8-OHdG) using enzyme-linked immunosorbent assay. Results: During univariate analysis stratified by gender, urinary ACR was significantly positively correlated with blood pressure and homeostasis model assessment of insulin resistance (HOMA-IR) in men and correlated with blood pressure, total cholesterol levels, triglyceride levels, LDL-cholesterol level, body mass index and urinary 8-OHdG in women. In the multivariate analysis adjusted for age and smoking, only HOMA-IR (p = 0.017) was an important influential factor of urinary ACR in men. On the contrary, urinary 8-OHdG (p = 0.010) was positively associated with urinary ACR in women. Conclusion: Oxidative stress may serve as a risk factor for the presence of albuminuria in Taiwanese women.
[Show abstract][Hide abstract] ABSTRACT: The level of C-reactive protein (CRP), an inflammatory biomarker that predicts future cardiovascular events, is a heritable trait that has been associated with variants of CRP and hepatic nuclear factor-1α (HNF1A) genes. Our aim was to test the statistical association between HNF1A genotypes/haplotypes and serum CRP level in Taiwanese.
A sample population of 617 Taiwanese subjects (all Han-Chinese origin) was enrolled. Five HNF1A single nucleotide polymorphisms (SNPs) rs1920792, rs1169288, rs7310409, rs2464196, rs1169310 were genotyped and analyzed.
After adjusting for clinical covariates, minor alleles of all the 5 study SNPs were associated with decreased CRP level (P=0.0078, P=0.0107, P=0.0006, P=0.0004 and P=0.0003, respectively). A common haplotype (TGATA) tagged by the minor alleles of study SNPs was associated with significantly decreased CRP level (P=0.0112). Subgroup analysis revealed that the association between HNF1A genotypes and CRP level occurred only in non-obese subjects.
HNF1A polymorphisms are independently associated with CRP level in Taiwanese. Further, HNF1A genotypes interact with obesity to set CRP level, revealing that genetic determinants for CRP level may be different between obese and non-obese individuals.
No preview · Article · Apr 2011 · Clinica chimica acta; international journal of clinical chemistry