Plasma α1-antitrypsin: a neglected predictor of angiographic severity in patients with stable angina pectoris / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As an acute phase protein, α1-antitrypsin (AAT) has been extensively studied in acute coronary syndrome, but it is unclear whether a relationship exists between AAT and stable angina pectoris (SAP). The purpose of the present study was to investigate the association between AAT plasma levels and SAP.</p><p><b>METHODS</b>Overall, 103 SAP patients diagnosed by coronary angiography and clinical manifestations and 118 control subjects matched for age and gender were enrolled in this case-control study. Plasma levels of AAT, high-sensitivity C-reactive protein (hsCRP), lipid profiles and other clinical parameters were assayed for all participants. The severity of coronary lesions was evaluated based on the Gensini score (GS) assessed by coronary angiography.</p><p><b>RESULTS</b>Positively correlated with the GS (r = 0.564, P < 0.001), the plasma AAT level in the SAP group was significantly higher than that in the control group (142.08 ± 19.61 mg/dl vs. 125.50 ± 19.67 mg/dl, P < 0.001). The plasma AAT level was an independent predictor for both SAP (odds ratio [OR] = 1.037, 95% confidence interval [CI]: 1.020-1.054, P < 0.001) and a high GS (OR = 1.087, 95% CI: 1.051-1.124, P < 0.001) in a multivariate logistic regression model. In the receiver operating characteristic curve analysis, plasma AAT level was found to have a larger area under the curve (AUC) for predicting a high GS (AUC = 0.858, 95% CI: 0.788-0.929, P < 0.001) than that of hsCRP (AUC = 0.665, 95% CI: 0.557-0.773, P = 0.006; Z = 2.9363, P < 0.001), with an optimal cut-off value of 137.85 mg/dl (sensitivity: 94.3%, specificity: 68.2%).</p><p><b>CONCLUSIONS</b>Plasma AAT levels correlate with both the presence and severity of coronary stenosis in patients with SAP, suggesting that it could be a potential predictive marker of severe stenosis in SAP patients.</p>

The relationship between serum amyloid A and apolipoprotein A-I in high-density lipoprotein isolated from patients with coronary heart disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alteration in the protein composition of high-density lipoprotein (HDL) has been proposed as a mechanism for the development of coronary heart disease (CHD). In HDL, an increase in serum amyloid A protein (SAA) accompanying the decrease in apolipoprotein A-I (apoA-I) has been found during the acute inflammation period. However, whether this phenomenon persists in CHD patients, a disease related to inflammation, is unknown. The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients.</p><p><b>METHODS</b>Overall, 98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study. Potassium bromide (KBr) density gradient ultracentrifugation was used to isolate HDL from plasma. The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits. Pearson's correlation and general linear models were used in the analysis.</p><p><b>RESULTS</b>Compared with controls, patients with CHD had a significant decrease in the amount of apoA-I ((14.21 ± 8.44) µg/ml vs. (10.95 ± 5.95) µg/ml, P = 0.003) in HDL and a significant increase in the amount of log SAA (1.21 ± 0.46 vs. 1.51 ± 0.55, P < 0.00001). Differences were independent of age, body mass index (BMI), HDL cholesterol (HDL-C), and other factors. An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group (β = 2.0, P = 0.026). In the general linear model, changes in log(SAA), age, age2, gender, BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I.</p><p><b>CONCLUSIONS</b>This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients, indicating the alteration of protein composition in HDL. However, the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.</p>

A multi-center, double-blind, randomized, parallel group study to evaluate the effects of two different doses of losartan on morbidity and mortality in Chinese patients with symptomatic heart failure intolerant of angiotensin converting enzyme inhibitor treatment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There have been no mortality/morbidity endpoint studies with losartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose losartan on clinical outcomes in Chinese subjects with heart failure.</p><p><b>METHODS</b>This study was a post hoc analysis of the Heart failure Endpoint evaluation of Angiotensin II Antagonist losartan (HEAAL) trial (n = 545). Chinese adults with symptomatic heart failure (New York Heart Association (NYHA) II-IV) intolerant of treatment with angiotensin converting enzyme (ACE) inhibitors were randomized to losartan 150 mg or 50 mg daily. The primary endpoint was the composite event rate of all-cause death or hospitalization for heart failure. Safety and tolerability were assessed.</p><p><b>RESULTS</b>Median follow-up was 4.8 years. Baseline characteristics were generally similar to the overall HEAAL cohort. Overall, 120 (44.1%) subjects in the losartan 150 mg group and 137 (50.2%) subjects in the losartan 50 mg group died (any cause) or were hospitalized for heart failure (hazard ratio (OR) 0.807, 95%CI 0.631 - 1.031). There were no notable differences between treatment groups in the proportion of subjects with adverse experiences.</p><p><b>CONCLUSION</b>The results of this post hoc analysis in Chinese subjects, although not powered to show significance, were generally consistent with the main study results, which demonstrated a significantly reduced risk of all cause death or hospitalization for heart failure with daily losartan 150 mg vs. losartan 50 mg in subjects with symptomatic heart failure and intolerance to ACE inhibitors, supporting the use of the higher dose for optimum clinical benefit.</p>

Modeling of systolic blood pressure reaction to antihypertensive agents in people with hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>We used the individual patient data from clinical trials, pooled in the INDANA data set, to explore whether blood pressure reduction was related to the baseline individual characteristics, and quantify the potential associations.</p><p><b>METHODS</b>We used the data from 31 140 patients with essential hypertension recruited in four randomized placebo-controlled clinical trials, MRC35-64, MRC65-74, STEP and SYST-EU. Thiazide diuretics, β-blocker, and calcium channel blocker, three of six major BP lowering drugs were analyzed. Patients were all with the same first dosage of the drug in each trial. Age, body weight, height, level of total cholesterin (TC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) when initialed and at first visit of follow-up, pharmacological treatment, gender, status of smoking, history of myocardium infarction were factors taken into model. Data were managed by software SAS(®). Statistical analyses were performed with SAS(®) and R. Model was developed to evaluate the relationship between decrease of SBP and characteristics of patients.</p><p><b>RESULTS</b>Initial SBP is the only modifier of treatment effect on SBP response in the 3 BP lowering drug classes (β = 0.09, 0.37 and 0.18, respectively). Age and initial DBP were factors significantly correlated with SBP fall for diuretic (β = 0.17 and 0.14), and age was one of factors significantly correlated with SBP fall for β-blocker (β = -0.17). Smokers would receive less SBP fall compare to non-smokers in β-blocker active treated group (β = -2.07). There is converse effect of age between the diuretic and β-blocker; older people seem sensitive to diuretic, while young people are sensitive to β-blocker. As to calcium channel antagonist class, body weight is another modifier (β = 0.06) (All P value are 0.000 except 0.050 for body weight in calcium channel antagonist class).</p><p><b>CONCLUSION</b>We identified 5 significant modifiers (baseline SBP and DBP, age, smoking status and body weight) for SBP response to treatment effect, while gender, TC and history of myocardial infarction are not modifiers for SBP response to treatment effect.</p>

Comparison of benazepril monotherapy to amlodipine plus benazepril in the treatment of patients with mild and moderate hypertension: a multicentre, randomized, double-blind, parallel-controlled study / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring.</p><p><b>METHODS</b>In a multicenter, randomized, double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP) remained ≥ 90 mm Hg (1 mm Hg = 0.133 kPa) were randomly divided into benazepril 10 mg/amlodipine 5 mg (BZ10/AML5) fixed-dose combination therapy group (once a day, n = 113), and benazepril monotherapy group (daily 20 mg, n = 107). In the two groups the patients with SeDBP ≥ 90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks, and the patients with SeDBP < 90 mm Hg remained the initial regimen for additional 4 weeks. The primary endpoint was to evaluate the improvement of SeDBP at the end of 8-week treatment. There were 74 patients (the combination therapy group n = 38, monotherapy therapy group n = 36) completed the 24 h ambulatory blood pressure monitoring which was included in the final efficacy analysis.</p><p><b>RESULTS</b>The randomized, double-blind treatment for 8 weeks, the mean value of SeDBP reduction, the reaching target blood pressure rate and total successful response rate to the treatment (a SeDBP < 90 mm Hg or a decrease of 10 mm Hg or more from baseline) were (11.7 ± 6.8) mm Hg, 65.7% and 88.5% in the combination therapy group, respectively, and were (7.7 ± 6.9) mm Hg, 35.5% and 65.5% in the monotherapy group, respectively. There were statistically significant difference between the combination therapy and the monotherapy groups in all the 3 indexs (P < 0.001). The fixed combination significantly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) values throughout the 24 h. The trough to peak ratios of DBP/SBP in the fixed compound of benazepril/amlodipine (10 mg/5 mg) and benazepril (20 mg) alone were 83.1%/76.0% and 85.8%/79.5%, respectively. Adverse events rates were 16.8% in the combination therapy group and 35.5% in the monotherapy group (P < 0.001).</p><p><b>CONCLUSIONS</b>The combination therapy with benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.</p>

Clinical features and prognosis of 188 Chinese patients with apical hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics and prognosis of Chinese patients with apical hypertrophic cardiomyopathy (AHCM).</p><p><b>METHODS</b>A total of 188 patients with AHCM diagnosed at Fuwai Hospital were included in this retrospective study. Clinical characteristics, mortality and cardiovascular morbidity were analyzed. A multiple logistic regression was performed to adjust for potential confounding factors.</p><p><b>RESULTS</b>Males predominated with a number of 139 (73.9%) in this cohort. Patient's age ranged from 15 to 81 (51.9 ± 12.6) years. There were 120 patients (63.8%) with "pure" type and 68 patients (36.2%) with "mixed" type of AHCM, 171 patients were followed up for (5.0 ± 3.0) years, cardiovascular mortality was 1.2%, 28 patients (16.4%) experienced one or more cardiovascular events.</p><p><b>CONCLUSION</b>The prevalence of AHCM is high in Chinese HCM patients, pure type AHCM is more common, and AHCM patients have a benign clinical course.</p>

High-density lipoprotein associated factors apoA-I and serum amyloid A in Chinese non-diabetic patients with coronary heart disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>High-density lipoprotein cholesterol (HDL-C) levels are a strong, independent inverse predictor of coronary heart disease (CHD). In this cross-sectional study we investigated the interrelationships between HDL-C and HDL related factors apolipoprotein A-I (apoA-I) and serum amyloid A (SAA) and the presence and extent of CHD in a population of Chinese patients with CHD.</p><p><b>METHODS</b>Two hundred and twenty-four consecutive patients took part in this study. Demographic data were obtained from hospital records. Serum chemical concentrations were measured by standard laboratory methods.</p><p><b>RESULTS</b>The concentrations of high-sensitive C-reactive protein (hsCRP) (median: 1.85 mg/L) and SAA (median: 9.40 mg/L) were significantly higher in the CHD group (P < 0.05), while concentrations of HDL-C ((1.03 +/- 0.25) mmol/L) and apoA-I ((604.59 +/- 105.79) mmol/L) were significantly lower than those in the non-CHD group (P < 0.05). The concentrations of apoA-I decreased with the increase in vascular damage, but the difference did not reach statistical significance. However, the concentrations of hsCRP and SAA increased with the increase in vascular damage. The unadjusted odd ratios (ORs) (CI) for apoA-I and SAA of the presence of CHD were 0.093 (0.990 - 0.997) (P = 0.00) and 2.571 (1.029 - 6.424) (P < 0.05), respectively. The association between elevated SAA and the presence of CHD was lost after adjusting for lipid status parameter concentrations. The associations between apoA-I, SAA and the extent of CHD remained strong, regardless of confounding variables.</p><p><b>CONCLUSIONS</b>Increased concentrations of SAA represent the inflammatory marker of the extent of coronary stenosis in patients with CHD. In contrast to SAA, the level of apoA-I was also associated with the presence of CHD, indicating that apoA-I was not only a marker of CHD presence but also a quantitative indicator of CHD extent. In short, determining the change apolipoprotein content within HDL particle is a more accurate and effective method to evaluate the impact of HDL on CHD.</p>

Angiotensin-converting enzyme gene I/D genotype affected metoprolol-induced reduction in 24-hour average heart rate / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Genetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in beta1-adrenergic receptor and blood pressure (BP), little was known about the association of angiotensin-converting enzyme (ACE) genotype with the therapeutic result of metoprolol. The present study aimed to investigate whether the ACE gene insertion (I)/deletion (D) polymorphism is related to the response to metoprolol in Chinese Han hypertensive patients.</p><p><b>METHODS</b>Ninety-six patients with essential hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks. Twenty-four hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed before and after treatment. Genotyping analysis was performed using PCR. The association of the ACE gene I/D polymorphism with variations in BP and heart rate (HR) was observed after the 8-week treatment.</p><p><b>RESULTS</b>The patients with ACE gene II polymorphism showed greater reduction in 24-hour average HR than those with ID or DD polymorphisms (P = 0.045), no effect of this genotype on the reduction in seating HR or in BP was observed. After adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene I/D polymorphism was still an independent predictor for variations in 24-hour average HR.</p><p><b>CONCLUSIONS</b>The II polymorphism in ACE gene could be a candidate predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive patients treated by metoprolol. Greater benefits would be obtained by patients with II polymorphism from the treatment with metoprolol. Larger studies are warranted to validate this finding.</p>

VKORC1 genotypes are associated with response to warfarin but free warfarin concentration during initial anticoagulation in healthy Chinese volunteers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The genetic variations in VKORC1 modulate the stable responses to warfarin administration. But the role of VKORC1 polymorphisms during the initial anticoagulation and elimination period in the Han Chinese population is not clear.</p><p><b>METHODS</b>Twenty-four healthy Chinese volunteers were grouped according to their VKORC1 genotype. Twelve subjects were in the 3 mg group and 12 in the 6 mg group. VKORC1 genotypes were determined by a polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) assay and sequencing. The international normalized ratio (INR) was measured with an ACL9000 coagulation analyser. Plasma free warfarin concentration was measured with LC/MS/MS.</p><p><b>RESULTS</b>In the initial anticoagulation period, the -1639AG and 1173TC carriers compared with the -1639AA and 1173TT carriers had a low INR value. The differences between genotypes with regard to INR values were more obvious in the 3 mg subjects (P < 0.05), and were not significantly different among the 6 mg subjects (P > 0.05). On the contrary, no significant difference of plasma free warfarin concentration between genotypes was observed in each dosage group. It took 96 hours for the INR value and 144 hours for the free warfarin plasma concentration to come back to baselines after the last dose. No significant difference among genotypes and dosing groups was detected in the elimination phase (P > 0.05).</p><p><b>CONCLUSION</b>VKORC1 polymorphisms are associated with differences in the initial response to warfarin when given at fixed doses, without affecting, as expected, its plasma concentration.</p>

Rapid response to lipids profile and leukocyte gene expression after rosuvastatin administration in Chinese healthy volunteers / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Statins are potent lipid-lowering agents widely used in medical practice. There has been growing evidence suggesting the pleiotropic effects of statins in addition to the lipid-lowering effect. However, it is still unclear how rapidly the beneficial effects of statins occur. The transcriptome of peripheral blood cells can be used as a sensor to drug therapy. The purpose of the study was to investigate the acute effects of rosuvastatin both on lipids profile and gene expression of peripheral leukocytes following therapy with a single dose of rosuvastatin.</p><p><b>METHODS</b>Thirty healthy Chinese male volunteers were enrolled. The serum lipids, high-sensitivity C-reactive protein, and plasma fibrinogen were determined before and 72 hours after administration of 20 mg of rosuvastatin. The differentially expressed genes of peripheral leukocytes after administration of rosuvastatin were screened using human oligonucleotide microarray gene expression chips. Then four of the differentially expressed genes including ATM, CASP8, IL8RB and S100B were verified by real-time polymerase chain reaction (PCR).</p><p><b>RESULTS</b>Rosuvastatin decreased both serum total cholesterol and low-density lipoprotein cholesterol significantly 72 hours after administration of a single dose of 20 mg rosuvastatin. However, no significant changes occurred in blood high-density lipoprotein cholesterol, triglycerides, C-reactive protein and fibrinogen after the treatment. A total of 24 genes were differentially expressed after the treatment. They were involved in important cell biological processes such as cytokine-cytokine receptor interaction, apoptosis signaling, etc.</p><p><b>CONCLUSIONS</b>Rosuvastatin rapidly modulates the serum lipids and affects the gene expression of peripheral leukocytes in healthy volunteers. This finding provides some new clues for further studies on its potential pleiotropic effects.</p>

Effect of arotinolol on left ventricular function in patients with idiopathic dilated cardiomyopathy / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of long-term treatment with arotinolol in patients with idiopathic dilated cardiomyopathy (IDCM).</p><p><b>METHODS</b>Sixty-three patients with IDCM were evaluated at baseline and after 12-month therapy with arotinolol. The conventional therapy for congestive heart failure was continued throughout the study with arotinolol as the only beta-blocker. Left ventricular function was assessed with the New York Heart Association functional class and two-dimensional echocardiography.</p><p><b>RESULTS</b>After 12-month arotinolol treatment, there was a significant improvement in left ventricular systolic function. Left ventricular end-systolic dimension significantly decreased from 59.52 +/- 8.83 mm to 50.89 +/- 8.17 mm (P < 0.001). Left ventricular ejection fraction significantly increased from 27.39% +/- 7.94% to 41.13% +/- 9.45% ( P < 0.001). Left ventricular mass index decreased from 150.47 +/- 42.42 g/m2 to 141.58 +/- 34.36 g/m2 (P < 0.01). No adverse events leading to premature discontinuation of study drug occurred.</p><p><b>CONCLUSION</b>In this preliminary study, 12-month arotinolol treatment has a favorable effect on left ventricular function in patients with IDCM, and it is safe and well tolerated.</p>

Efficacy of monotherapy with 15 antihypertensive agents in treating essential hypertension assessed by 24-hour ambulatory blood pressure monitoring / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the efficacy of the monotherapy of 15 agents in treating essential hypertension.</p><p><b>METHODS</b>After 2-week wash-out, a total of 370 patients with seated diastolic blood pressure 95-114 mmHg and seated systolic blood pressure < 180 mmHg were randomized to different therapeutic groups. 24-hour ambulatory blood pressure monitoring was performed before medication and at the end of 8 weeks.</p><p><b>RESULT</b>All the agents significantly reduced the 24 hour mean blood pressures after treatment except doxazosin, terazosin, and torasemide.</p><p><b>CONCLUSION</b>The result suggested that the angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers and long-acting calcium antagonists were effective in treating essential hypertension, while the low-dose doxazosin, terazosin and torasemide can be used for combination therapy but not for monotherapy.</p>

Prognostic value of N-terminal-pro-brain natriuretic peptide on admission in patients with chronic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>Heart failure is responsible for a huge burden in hospital care. Our goal was to evaluate the value of N-terminal-pro-brain natriuretic peptide (Nt-proBNP) on predicting death or hospital readmission after hospital discharge in patients with chronic heart failure (CHF).</p><p><b>METHODS</b>From March 2003 to April 2005, 135 consecutive patients (97 male and 38 female, mean age 60.7 years +/- 13.1 years) with chronic heart failure [dilated cardiomyopathy (44%) and coronary heart disease (35%)] were included in this study. Plasma concentrations of the Nt-proBNP were measured by ELISA on admission. All patients received conventional therapy and were followed up for 24 months. The primary end point was death or readmission.</p><p><b>RESULTS</b>(1) During the follow up period (640 days +/- 100 days), 11 patients died and 39 patients rehospitalized, the median Nt-proBNP level on admission was significantly higher in patients died during the follow up period (5908 ng/L) than that of rehospitalized patients (2768 ng/L, P = 0.038). Plasma Nt-proBNP level on admission were significantly higher in primary end point group (n = 50, 2947 ng/L) than that in non-primary end point group (n = 85, 917 ng/L, P < 0.01). (2) Variables associated with an increased hazard of death and/or rehospitalization were Nt-proBNP and NYHA degree when analyzed by logistic regression models. Increased Log Nt-proBNP was the strongest independent predictor of an adverse outcome of CHF (odds ratio 13.8, 95% confidence interval 2.29 to 2.78, P < 0.01). (3) Area under the curve for Nt-proBNP in evaluating prognosis of CHF patients was 0.885 (positive predictive value 88.5%, negative predictive value 11.5%).</p><p><b>CONCLUSION</b>Nt-proBNP level on admission is a strong predictor of rehospitalization and death within 24 months after hospital discharge in patients with chronic heart failure.</p>

The association of single nucleotide polymorphism of slow delayed rectifier K+ channel genes with atrial fibrillation in Han nationality Chinese / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between atrial fibrillation and the single nucleotide polymorphism (SNP) of slow delayed rectifier K(+) channel (I(Ks)) genes in Han nationality Chinese.</p><p><b>METHODS</b>Three hundred and eighty of Han nationality Chinese (142 atrial fibrillation, 120 in-hospital and 118 out-hospital control) were enrolled in this study. Asian specific non-synonymous SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N were genotyped by restriction fragment length polymorphism analysis. A newly cloned KCNE4 gene was also screened for any possible SNP.</p><p><b>RESULTS</b>The minor allele frequency of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N in out-hospital subjects was 0.079, 0, 0.042, 0.317 and 0.004, respectively. None of these SNPs was relationed with any atrial fibrillation phenotype. A KCNE4 E145D was discovered and proven statistically to relation significantly to atrial fibrillation by logistic regression analysis (OR = 1.66, P = 0.044). The minor allele frequency of KCNE4 E145D was as high as 0.271 in out-hospital subjects.</p><p><b>CONCLUSIONS</b>None of the SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N was associated with atrial fibrillation phenotype, but KCNE4 E145D may relation to atrial fibrillation. The effect of KCNE4 E145D variation on the function of I(Ks) channel is to be determined.</p>