Humans ; Atrial Fibrillation/genetics* ; Epigenesis, Genetic

Atrial Fibrillation ; epidemiology ; genetics ; therapy ; Catheter Ablation ; China ; epidemiology ; Humans

G protein-coupled inward rectifier K(+) channel 4(GIRK4) is a G protein-coupled inward rectifier potassium channel family member. Encoded by the KCNJ5, it is widely distributed in the mammalian heart, brain, and other tissues and organs. Recent studies have demonstrated that the abnormal expression of GIRK4 gene is associated with atrial fibrillation, and meanwhile may be closely related to obesity, metabolic syndrome, and many other clinical conditions. Further research on the role the GIRK4 gene in the pathophysiology of these clinical conditions will definitely facilitate their clinical diagnosis and treatment.
Atrial Fibrillation ; genetics ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; genetics ; Humans ; Metabolic Syndrome ; genetics

Arrhythmias, Cardiac ; complications ; genetics ; physiopathology ; Atrial Fibrillation ; complications ; genetics ; physiopathology ; Electrophysiology ; Humans

Anticoagulants ; therapeutic use ; Atrial Fibrillation ; etiology ; genetics ; therapy ; Catheter Ablation ; Humans ; Thromboembolism ; prevention & control ; United States

OBJECTIVETo investigate the mRNA and protein expression of mineralocorticoid receptor (MR) in patients with atrial fibrillation.

METHODSTwenty-five patients with rheumatic heart valve disease, 12 in sinus rhythm and 13 in chronic atrial fibrillation (>or= 6 months), underwent transthoracic echocardiography and right and left atrial lateral wall tissue samples were obtained from these patients during mitral/aortic valve replacement operation. Realtime quantitative PCR and Western blot were used to determine the mRNA and protein expression of MR in atria specimens. The distribution of MR in human atria was analyzed by specific immunohistochemical staining.

RESULTSThe left atrial diameters increased markedly in atrial fibrillation group compared with that in sinus rhythm group (P<0.01). And the results showed that the level of mRNA and protein of MR were increased significantly in atrial fibrillation group compared with those in sinus rhythm group (P<0.01 or 0.05), whereas the expression of mRNA and protein of MR were found to be no difference between left atria and right atria both in fibrillation and sinus groups (all P>0.05). The special immunohistochemical staining demonstrated that MR was abundant in the human atrial myocardium and MRs were located mainly in the cytoplasm of atrial cells, which were more evident in atrial fibrillation group than those in sinus rhythm group.

CONCLUSIONThese findings suggested that MRs were upregulated in atrial fibrillation and aldosterone antagonists may be effective in treating atrial fibrillation.

Adult ; Atrial Fibrillation ; metabolism ; Humans ; Male ; Middle Aged ; Myocardium ; metabolism ; RNA, Messenger ; genetics ; Receptors, Mineralocorticoid ; metabolism

OBJECTIVETo assess the association of KCNE1 (rs1805127) and KCNE4 (rs12621643) polymorphisms with atrial fibrillation (AF) among ethnic Uygur and Han Chinese in Xinjiang.

METHODSA case-control study was carried out. The patients and controls were selected based on ethnicity, gender and age with an 1:1 ratio. DNA was extracted from peripheral blood samples. Genotypes of KCNE1 (rs1805127) and KCNE4 (rs12621643) were determined with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.

RESULTSMultivariate Logistic regression analysis showed KCNE1 (rs1805127) to be an independent risk factor for AF among Uygurs, while KCNE4 (rs12621643) was a risk factor for both Uygur and Han patients with AF (P < 0.05). The population attributable risk percentage (PARc%) of obstructive sleep apnea hpoventilation syndrome, obesity, hypertension, cholesterol, Hcy, hs-CRP, IL-6, KCNE1 (rs1805127) and KCNE4 (rs12621643) were 9.68%, 12.06%, 15.76%, 6.91%, 11.37%, 17.78%, 9.31%, 11.27% and 6.46% among the Uygurs, respectively. The PARc% of drinking, hypertension, cholesterol, Hcy, hs-CRP, IL-6, and KCNE4 (rs12621643) were 12.94%, 14.48%, 7.24%, 8.49%, 17.29%, 9.49% and 7.41% among Hans.

CONCLUSIONThe KCNE1 (rs1805127) appears to an independent risk factor for AF in the Uygur population. And the KCNE4 (rs12621643) was an independent risk factor for AF among both Uygurs and Hans. Management of the risk factors of AF based on testing of "risk genes" may have an impact on the prevention and treatment of AF.

Atrial Fibrillation ; etiology ; genetics ; Case-Control Studies ; China ; ethnology ; Humans ; Polymorphism, Genetic ; Potassium Channels, Voltage-Gated ; genetics ; Risk Factors

BACKGROUNDGrowing epidemiologic evidence has indicated that genetics can predispose individuals to the occurrence of lone atrial fibrillation (AF). The angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with hypertension and left ventricular hypertrophy. The objective of our study was to investigate the association of ACE2 gene polymorphisms with lone AF.

METHODSA total of 265 consecutive lone AF patients and 289 healthy controls were successfully investigated. The polymorphisms rs2106809 and rs2285666 were genotyped by polymerase chain reaction (PCR) and direct sequencing. A Logistic regression model was used to determine the odds ratio (OR) and 95% confidence intervals (CI) of variations of ACE2 for lone AF.

RESULTSThe T allele of rs2106809 conferred an increased risk for lone AF (OR 1.24, 95% CI 1.01-1.52, P = 0.03) in males after adjustment for conventional risk factors. SNP at rs2285666 in males was not significantly different between AF patients and controls. No association was found between the two polymorphisms in the female population with lone AF. After (36.3 ± 4.5) months of follow-up, the end point data were obtained: death (cardiac and noncardiac), ischemic stroke, and heart failure. In the male subgroup, the associations between rs2106809 T male carriers and combined end points including ischemic stroke, heart failure, and death in our study were of significance (OR 3.6, 95% CI 1.0-13.1, P = 0.04).

CONCLUSIONSThe results indicate that polymorphism at ACE2 gene is associated with male lone AF in a Chinese Han population. Lone AF males who carry the rs2106809 T allele are associated with adverse cardiac events.

Aged ; Asian Continental Ancestry Group ; genetics ; Atrial Fibrillation ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; genetics

PURPOSE: Recently, mitochondrial DNA 4977bp deletion (mtDNA4977-mut), a somatic mutation related to oxidative stress, has been shown to be associated with atrial fibrillation (AF). We hypothesized that patient age, as well as electroanatomical characteristics of fibrillating left atrial (LA), vary depending on the presence of mtDNA4977-mut in peripheral blood among patients with non-valvular AF. MATERIALS AND METHODS: Analyzing clinical and electroanatomical characteristics, we investigated the presence of the mtDNA4977-mut in peripheral blood of 212 patients (51.1+/-13.2 years old, 83.5% male) undergoing catheter ablation for non-valvular AF, as well as 212 age-matched control subjects. RESULTS: The overall frequency of peripheral blood mtDNA4977-mut in patients with AF and controls was not significantly different (24.5% vs. 19.3%, p=0.197). When the AF patient group was stratified according to age, mtDNA4977-mut was more common (47.4% vs. 20.0%, p=0.019) in AF patients older than 65 years than their age-matched controls. Among AF patients, those with mtDNA4977-mut were older (58.1+/-11.9 years old vs. 48.8+/-11.9 years old, p<0.001). AF patients positive for the mtDNA mutation had greater LA dimension (p=0.014), higher mitral inflow peak velocity (E)/diastolic mitral annular velocity (Em) ratio (p<0.001), as well as lower endocardial voltage (p=0.035), and slower conduction velocity (p=0.048) in the posterior LA than those without the mutation. In multivariate analysis, E/Em ratio was found to be significantly associated with the presence of mtDNA4977-mut in peripheral blood. CONCLUSION: mtDNA4977-mut, an age-related somatic mutation detected in the peripheral blood, is associated with advanced age and electro-anatomical remodeling of the atrium in non-valvular AF.
Adult ; Aged ; Atrial Fibrillation/blood/*genetics/*physiopathology ; Atrial Remodeling/*genetics ; Base Pairing/*genetics ; Case-Control Studies ; DNA, Mitochondrial/*blood/*genetics ; Female ; Heart Atria/pathology/physiopathology ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Mutation Rate ; Phenotype ; Sequence Deletion/*genetics

OBJECTIVETo compare the changes of both inward rectifying K(+) (Kir) current(I(k1)) density and mRNA expression level of Kir2.1, a major subfamily of Kir in chronic human atrial fibrillation (CAF) with those in normal sinus rhythm (NSR).

METHODSI(k1) density was measured with whole-cell patch clamp technique in single myocyte isolated by an enzymatic dissociation method from right atrial appendages in patients with CAF (n = 8) and those with NSR (n = 12). The mRNA expression levels of Kir2.1 was determined in right atrial appendages from CAF (n = 19) and NSR (n = 18) by semiquantitative reverse-transcription polymerase chain reaction (RT-PCR).

RESULTThe average resting membrane potentials were similar between CAF and NSR (-78.95 mV +/- 4.67 mV and -70.22 mV +/- 11.08 mV, P>0.05). I(k1) density in single myocyte significantly increased at hyperpolarized potential level (-100 mV) in CAF compared to that in NSR (-9.59 pA/pF +/- 2.47 pA/pF vs. -5.58 pA/pF +/- 2.52 pA/pF, P<0.01). The mRNA level of Kir2.1 was also significantly higher in CAF than that of NSR (0.50+/-0.16 vs. 0.34+/-0.09, P<0.05).

CONCLUSIONThe data suggest that Kir2.1 up-regulation and I(k1) current increase might contribute to the electrical remodeling in CAF patients.

Atrial Fibrillation ; genetics ; metabolism ; physiopathology ; Gene Expression ; Humans ; Myocytes, Cardiac ; metabolism ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Inwardly Rectifying ; genetics ; metabolism ; RNA, Messenger ; genetics