Lack of association between rs3807989 in cav1 and atrial fibrillation.
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ABSTRACT:
SUBMITTER: Li G
PROVIDER: S-EPMC4129053 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
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Lack of association between rs3807989 in cav1 and atrial fibrillation.
Li Guocao G Zhang Rongfeng R Gao Lianjun L Zhang Shulong S Dong Yingxue Y Yin Xiaomeng X Chang Dong D Yang Yanzong Y Xia Yunlong Y
International journal of clinical and experimental pathology 20140615 7
<h4>Background</h4>A novel gene Caveolin-1(CAV1) was identified to be susceptibility to PR interval and also associated with atrial fibrillation (AF) in two Genome wide associations studies (GWAS) studies in European ancestry. The purpose of this study was to determine the association of the SNPs in CAV1 gene of rs3807989 with AF in Chinese Han patients.<h4>Methods and results</h4>We attempted a replication in a cohort of 839 Chinese AF patients and 1215 healthy controls using melting temperatur ...[more]
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Project description:BACKGROUND Atrial fibrillation (AF) is the most common sustained arrhythmia affected by multiple cardiovascular risk factors. It is reported that caveolin-1 gene (CAV1) rs3807989 polymorphism might be associated with AF risk. The goal of this meta-analysis was to confirm the association between CAV1 rs3807989 polymorphism and susceptibility to AF. MATERIAL AND METHODS We carried out a comprehensive literature search through the electronic databases PubMed, MEDLIN, and Web of Science. We performed a meta-analysis of all selected studies based on CAV1 rs3807989 polymorphism genotypes, including 3758 cases and 6126 controls. RESULTS After meta-analysis with fixed- or random-effects models, we found significant associations in all 5 comparisons: allelic model (G/A; OR=1.228, 95%CI: 1.061-1.420; P=0.006), homozygote model (GG/AA; OR=1.439, 95%CI: 1.094-1.894; P=0.009), heterozygote model (GG/GA; OR=1.257, 95%CI: 1.064-1.486; P=0.007), dominant model (GG/AA+GA; OR=1.287, 95%CI: 1.076-1.540; P=0.006), and recessive model (AA/GA+GG; OR=0.738, 95%CI: 0.629-0.867; P<0.001). Sensitivity analysis results revealed the overall results were robust. CONCLUSIONS The results revealed a significant association between CAV1 gene rs3807989 polymorphism and susceptibility to AF, suggesting that the presence of allelic G might be one of the genetic factors conferring susceptibility to AF. To confirm this association, further well-designed studies are necessary.
| S-EPMC5091217 | biostudies-literature
Project description:Recent genome-wide association studies (GWAS) in European ancestry populations revealed several genomic loci for atrial fibrillation (AF). We previously replicated the 4q25 locus (PITX2) and 16q22 locus (ZFHX3) in the Chinese population, but not the KCNN3 locus on 1q21. With single-nucleotide polymorphism rs3807989 in CAV1 encoding caveolin-1, however, controversial results were reported in 2 Chinese replication studies. Six remaining AF genetic loci from GWAS, including rs3807989/CAV1, rs593479/PRRX1, rs6479562/C9orf3, rs10824026/SYNPO2L, rs1152591/SYNE2, and rs7164883/HCN4, were analyzed in a Chinese Han population with 941 cases and 562 controls. Only rs3807989 showed significant association with AF (Padj=4.77×10(-5)), and the finding was replicated in 2 other independent populations with 709 cases and 2175 controls, 463 cases and 644 controls, and the combined population with a total of 2113 cases and 3381 controls (Padj=2.20×10(-9); odds ratio [OR]=1.34 for major allele G). Meta-analysis, together with data from previous reports in Chinese and Japanese populations, also showed a significant association between rs3807989 and AF (P=3.40×10(-4); OR=1.24 for allele G). We also found that rs3807989 showed a significant association with lone AF in 3 independent populations and in the combined population (Padj=3.85×10(-8); OR=1.43 for major allele G). The data in this study revealed a significant association between rs3807989 and AF in the Chinese Han population. Together with the findings that caveolin-1 interacts with potassium channels Kir2.1, KCNH2, and HCN4 and sodium channels Nav1.5 and Nav1.8, CAV1 becomes a strong candidate susceptibility gene for AF across different ethnic populations. This study is the first to show a significant association between rs3807989 and lone AF.
| S-EPMC4599427 | biostudies-literature
Project description:CONTEXT:Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. OBJECTIVE:To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors. DESIGN, SETTING, AND PARTICIPANTS:The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. MAIN OUTCOME MEASURES:Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ?65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. RESULTS:Across 11,971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P = .004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P = .51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P = .009). CONCLUSIONS:In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.
| S-EPMC3073054 | biostudies-literature
Project description:The mouse is a useful preclinical species for evaluating disease etiology due to the availability of a wide variety of genetically modified strains and the ability to perform disease-modifying manipulations. In order to establish an atrial filtration (AF) model in our laboratory, we profiled several commonly used murine AF models. We initially evaluated a pharmacological model of acute carbachol (CCh) treatment plus atrial burst pacing in C57BL/6 mice. In an effort to observe micro-reentrant circuits indicative of authentic AF, we employed optical mapping imaging in isolated mouse hearts. While CCh reduced atrial refractoriness and increased atrial tachyarrhythmia vulnerability, the left atrial (LA) excitation patterns were rather regular without reentrant circuits or wavelets. Therefore, the atrial tachyarrhythmia resembled high frequency atrial flutter, not typical AF per se. We next examined both a chronic angiotensin II (Ang II) infusion model and the surgical model of transverse aortic constriction (TAC), which have both been reported to induce atrial and ventricular structural changes that serve as a substrates for micro-reentrant AF. Although we observed some extent of atrial remodeling such as fibrosis or enlarged LA diameter, burst pacing-induced atrial tachyarrhythmia vulnerability did not differ from control mice in either model. This again suggested that an AF-like pathophysiology is difficult to demonstrate in the mouse. To continue searching for a valid murine AF model, we studied mice with a cardiac-specific deficiency (KO) in liver kinase B1 (Cardiac-LKB1), which has been reported to exhibit spontaneous AF. Indeed, the electrocardiograms (ECG) of conscious Cardiac-LKB1 KO mice exhibited no P waves and had irregular RR intervals, which are characteristics of AF. Histological evaluation of Cardiac-LKB1 KO mice revealed dilated and fibrotic atria, again consistent with AF. However, atrial electrograms and optical mapping revealed that electrical activity was limited to the sino-atrial node area with no electrical conduction into the atrial myocardium beyond. Thus, Cardiac-LKB1 KO mice have severe atrial myopathy or atrial standstill, but not AF. In summary, the atrial tachyarrhythmias we observed in the four murine models were distinct from typical human AF, which often exhibits micro- or macro-reentrant atrial circuits. Our results suggest that the four murine AF models we examined may not reflect human AF well, and raise a cautionary note for use of those murine models to study AF.
| S-EPMC8741011 | biostudies-literature
Project description:Oxidative stress (OS) may be a key mechanism underlying the development of atrial fibrillation (AF) in experimental studies, but data in humans remain limited.Systemic OS can be estimated by measurements of circulating levels of the aminothiols including glutathione, cysteine, and their oxidized products. We tested the hypothesis that the redox potentials of glutathione (EhGSH) and cysteine will be associated with prevalent and incident AF.Plasma levels of aminothiols were measured in 1439 patients undergoing coronary angiography, of whom 148 (10.3%) had a diagnosis of AF. After a median follow-up of 6.3 years, 104 of 917 patients (11.5%) developed incident AF. Multivariate logistic regression and Cox regression models were used to determine whether OS markers were independent predictors of prevalent and incident AF after adjustment for traditional risk factors, heart failure, coronary artery disease, and high-sensitivity C-reactive protein level.For each 10% increase in EhGSH, the odds of prevalent AF was 30% higher (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.1-1.7; P = .02) and 90% higher (OR 1.9; 95% CI 1.3-2.7; P = .004) when the median was used as a cutoff. The EhGSH level above the median was more predictive of chronic AF (OR 4.0; 95% CI 1.3-12.9; P = .01) than of paroxysmal AF (OR 1.7; 95% CI 1.1-2.7; P = .03). Each 10% increase in EhGSH level was associated with a 40% increase in the risk of incident AF (hazard ratio 1.4; 95% CI 1.1-1.7; P = .01).Increased OS measured by the redox potentials of glutathione is associated with prevalent and incident AF. Therapies that modulate OS need to be investigated to treat and prevent AF.
| S-EPMC5817893 | biostudies-literature
Project description:BackgroundThe association between atrial fibrillation (Afib) and sinus and AV nodal dysfunction has previously been reported. However, no data are available regarding the association between Afib and bundle branch block (BBB).MethodsPatient data were obtained from the Nationwide Inpatient Sample (NIS) database between years 2009 and 2015. Patients with a diagnosis of Afib and BBB were identified using validated International Classification of Diseases, 9th revision, and Clinical Modification (ICD-9-CM) codes. Statistical analysis using the chi-square test and multivariate linear regression analysis were performed to determine the association between Afib and BBB.ResultsThe total number of patients with BBB was 3,116,204 (1.5%). Patients with BBB had a mean age of 73.5 ± 13.5 years, 53.6% were males, 39.1% belonged to the age group ≥80 years, and 72.9% were Caucasians. The prevalence of Afib was higher in the BBB group, as compared to the non-BBB group (29% vs 11.8%, p value<.001). This association remained significant in multivariate regression analysis with an odds ratio of 1.25 (CI: 1.24-1.25, P < .001). Among the subtypes of BBB, Afib was comparatively more associated with RBBB (1.32, CI 1.31-1.33, p value<.0001) than LBBB (1.17, CI 1.16-1.18, p value<.0001). The mean cost was higher among Afib with BBB, compared with Afib patients without BBB ($15 795 vs $14 391, p value<.0001). There was no significant difference in the mean length of stay (5.6 vs 5.9 days, p value<.0001) or inpatient mortality (4.9% vs 4.8%).ConclusionThis study demonstrates that prevalence of Afib is higher in patients with BBB than without BBB. Cost are higher for Afib patients with BBB, compared to those without BBB, with no significant increase in mortality or length of stay.
| S-EPMC8339096 | biostudies-literature
Project description:BackgroundThe most prevalent sustained arrhythmia in medical practice, atrial fibrillation (AF) is closely associated with a high risk of cardiovascular disease. Nevertheless, the risk of AF associated with cardiovascular risk factors has not been well elucidated. We pooled all published studies to provide a better depiction of the relationship among cardiovascular risk factors with AF.MethodsStudies were searched in the MEDLINE, Web of Science, and EMBASE databases since initiation until January 15, 2022. Prospective cohort studies assessing the relationship a minimum of single cardiovascular risk factors to AF incidence were included if they contained adequate data for obtaining relative risks (RR) and 95% confidence intervals (CI). Random-effects models were utilized to perform independent meta-analyses on each cardiovascular risk factor. PROSPERO registry number: CRD42022310882.ResultsA total of 17,098,955 individuals and 738,843 incident cases were reported for data from 101 studies included in the analysis. In all, the risk of AF was 1.39 (95% CI, 1.30-1.49) for obesity, 1.27 (95% CI, 1.22-1.32) per 5 kg/m2 for increase in body mass index, 1.19 (95% CI, 1.10-1.28) for former smokers, 1.23 (95% CI, 1.09-1.38) for current smokers, 1.31 (95% CI, 1.23-1.39) for diabetes mellitus, 1.68 (95% CI, 1.51-1.87) for hypertension, and 1.12 (95% CI, 0.95-1.32) for dyslipidemia.InterpretationAdverse cardiovascular risk factors correlate with an increased risk of AF, yet dyslipidemia does not increase the risk of AF in the general population, potentially providing new insights for AF screening strategies among patients with these risk factors.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, PROSPERO identifier (CRD42022310882).
| S-EPMC10518410 | biostudies-literature
Project description:Background: A potential evidence from previous epidemiological studies remains conflicting findings regarding the association between atrial fibrillation (AF) and dementia risk. We, therefore, carried out a meta-analysis of relevant studies to investigate the magnitude of the association between AF and dementia risk. Methods: We performed a systematic literature search of PubMed, EMBASE, and Google Scholar for potential studies between January 1, 1990, and December 31, 2018, with no restriction on the publication language. All potential studies were independently assessed by two reviewers. We only included observational studies that calculated the odds ratio (OR)/hazards ratio (HR) for dementia associated with atrial fibrillation. We first assessed the heterogeneity among study-specific HRs using the Q statistic and I 2 statistic. We then used the random-effects model to obtain the overall HR and its 95% CI for all studies. We also tested and corrected for publication bias by funnel plot-based methods. The quality of each study was assessed with the Newcastle Ottawa Scale. Results: A total of 16 studies with 2,415,356 individuals, and approximately 200,653 cases of incidence dementia were included in this study. Patients with AF had a greater risk of incidence dementia than those without AF (random-effect hazard ratio HR: 1.36, 95% CI: 1.23-1.51, p < 0.0001; I 2 = 83.58). Funnel plot and Egger test did not reveal significant publication bias. However, limitations of the study included high heterogeneity and varying degrees of confounder adjustment across individual studies. Conclusion: This study serves as added evidence supporting the hypothesis that AF is associated with an increased risk of dementia. More studies are needed to establish whether optimal treatment of AF can reduce or mitigate the risk of dementia.
| S-EPMC6857071 | biostudies-literature
Project description:BackgroundBlacks have a lower risk of atrial fibrillation (AF) despite having more AF risk factors, but the mechanism remains unknown. Premature atrial contraction (PAC) burden is a recently identified risk factor for AF.ObjectiveThe purpose of this study was to determine whether the burden of PACs explains racial differences in AF risk.MethodsPAC burden (number per hour) was assessed by 24-hour ambulatory electrocardiographic (ECG) monitoring in a randomly selected subset of patients in the Cardiovascular Health Study. Participants were followed prospectively for the development of AF, diagnosed by study ECG and hospital admission records.ResultsAmong 938 participants (median age 73 years; 34% black; 58% female), 206 (22%) developed AF over a median follow-up of 11.0 years (interquartile range 6.1-13.4). After adjusting for age, sex, body mass index, coronary disease, congestive heart failure, diabetes, hypertension, alcohol consumption, smoking status, and study site, black race was associated with a 42% lower risk of AF (hazard ratio 0.58, 95% confidence interval [CI] 0.40-0.85; P = .005). The baseline PAC burden was 2.10 times (95% CI 1.57-2.83; P <.001) higher in whites than blacks. There was no detectable difference in premature ventricular contraction (PVC) burden by race. PAC burden mediated 19.5% (95% CI 6.3-52.5) of the adjusted association between race and AF.ConclusionOn average, whites exhibited more PACs than blacks, and this difference statistically explains a modest proportion of the differential risk of AF by race. The differential PAC burden, without differences in PVCs, by race suggests that identifiable common exposures or genetic influences might be important to atrial pathophysiology.
| S-EPMC5712237 | biostudies-literature
Project description:Background:The interaction between cardiorespiratory fitness (CRF) and incidence of atrial fibrillation (AF) and the interaction between obesity and incidence of AF have been explored separately. Therefore, we evaluated the association between CRF, body mass index (BMI), and risk of developing AF in a cohort of middle-aged and older US Veterans. Methods:Symptom limited exercise tests (ETT) were conducted among 16,397 Veterans (97% male) from January 9,1987 to December 31,2017. No history of AF was evident at the time of the ETTs. CRF was expressed as quartiles of peak metabolic equivalents (METs) achieved within each age decile. Weight status was classified as normal (BMI < 25 kg/m2), overweight (BMI 25-30 kg/m2), obese (BMI 30-35 kg/m2), or severely obese (BMI > 35 kg/m2). Multivariable Cox proportional hazards regression models were used to compare the association between BMI, CRF categories, and incidence of AF. Results:Over a median follow-up of 10.7 years, 2,155 (13.1%) developed AF. Obese and severely obese subjects had 13% and 32% higher risks for incidence of AF, respectively, vs. normal weight subjects. Overweight and obese subjects in the most fit quartile had 50% decline in AF risk compared to the least-fit subjects. Severely obese subjects had marked increases in AF risk (~50-60%) regardless of fitness level. Risk of developing AF increases with higher BMI and lower CRF. Conclusion:Improving CRF should be advocated when assessing those at risk for developing AF.
| S-EPMC7596185 | biostudies-literature