Background A polymorphism consisting of a C825T substitution in the G protein β3 subunit gene (GNB3) has been associated with enhanced human atrial inward r ectifier potassium currents regarding the TT genotype. Ther...Background A polymorphism consisting of a C825T substitution in the G protein β3 subunit gene (GNB3) has been associated with enhanced human atrial inward r ectifier potassium currents regarding the TT genotype. Therefore, we investigate d a possible impact of the GNB3 C825T polymorphismon atrial fibrillation in an a ssociation study. Methods Two hundred ninety one consecutive patients admitted to our center with atrial fibrillation (age, 58±10 years) and 292 consecutive c ontrol patients without atrial tachyarrhythmias (59±11 years) were genotyped fo r the C825T polymorphism. Patients with coronary heart disease, valvular heart d isease, or cardiomyopathy were excluded from the study. Both patient groups had a similar incidence of cardiovascular risk factors (hypertension, hypercholester olemia, body mass index). Results The prevalence of the GNB3 TT genotype was sig nificantly lower in patients with atrial fibrillation(5.8%) than in the control group(12.0%); however, no significant differences in the frequencies of the CT and CC genotypes were found. The TT genotype was associated with a 54%decrease in the adjusted risk (OR from a multivariant model, 0.46; 95%CI, 0.24 to 0.87; P=.02) for the occurrence of atrial fibrillation. Conclusions The current study suggests an association between the GNB3 TT genotype and a reduced risk for the occurrence of atrial fibrillation.展开更多
文摘Background A polymorphism consisting of a C825T substitution in the G protein β3 subunit gene (GNB3) has been associated with enhanced human atrial inward r ectifier potassium currents regarding the TT genotype. Therefore, we investigate d a possible impact of the GNB3 C825T polymorphismon atrial fibrillation in an a ssociation study. Methods Two hundred ninety one consecutive patients admitted to our center with atrial fibrillation (age, 58±10 years) and 292 consecutive c ontrol patients without atrial tachyarrhythmias (59±11 years) were genotyped fo r the C825T polymorphism. Patients with coronary heart disease, valvular heart d isease, or cardiomyopathy were excluded from the study. Both patient groups had a similar incidence of cardiovascular risk factors (hypertension, hypercholester olemia, body mass index). Results The prevalence of the GNB3 TT genotype was sig nificantly lower in patients with atrial fibrillation(5.8%) than in the control group(12.0%); however, no significant differences in the frequencies of the CT and CC genotypes were found. The TT genotype was associated with a 54%decrease in the adjusted risk (OR from a multivariant model, 0.46; 95%CI, 0.24 to 0.87; P=.02) for the occurrence of atrial fibrillation. Conclusions The current study suggests an association between the GNB3 TT genotype and a reduced risk for the occurrence of atrial fibrillation.
文摘血管平滑肌（VSM）细胞和内皮细胞（EC）都表达K^＋通道，微血管平滑肌细胞至少表达4种不同类别的K^＋通道，内向整流性钾通道[inward rectifier K^＋（KIR）channel]；ATP敏感性钾通道[（ATP—sensitive K^＋（KATP）channel]；电压门控式钾通道[vohage—gated K^＋（Kv）channel]；大电导钙激活钾通道[the large conductance，Ca^2＋-activated K K^＋（MaxiK，BKCa）channel]。
基金supported by the National Natural Science Foundation of China(No.30871008 and 81370306Open Research Fund Program of Hubei Provincial Key Laboratory of Biological Targeting Therapy,China(No.2007B04)
文摘本文旨在建立转基因联合抑制心脏钙/钙调素依赖性蛋白激酶II(Ca2+/calmodulin-dependent protein kinase II,Ca MKII)及内向整流性钾电流(Ik1)小鼠模型,初步探讨该联合抑制在基础和应激状态下对小鼠心脏电生理、结构与功能重构的影响。将动物分为4组:野生组(WT),转基因Ca MKII抑制组(AC3-I),转基因Ik1抑制组(Kir2.1-AAA),转基因联合抑制组(AC3-I+Kir2.1-AAA)。记录各组动物在基础状态下及注射异丙肾上腺素后的心电图;同时分别对各组动物进行心脏超声检查,以了解心脏重构情况;在酶解法分离单个左室心肌细胞后,采用全细胞膜片钳法记录心肌细胞Ik1和瞬间外向钾电流(Ito)。实验结果显示:在基础状态下,心电图显示各组动物之间的心率、PR间期和QRS间期均无显著差别;注射异丙基肾上腺素后,上述心电图指标和小鼠发生室性心律失常的情况在各组间也无显著差别;4组小鼠间M型(Motion-mode)和二维超声检测的各项指标无显著差异;全细胞膜片钳实验结果表明,AC3-I组动物心肌细胞的Ik1电流密度最大(P<0.01),WT组的次之(P<0.01),其他两组较WT组显著降低(P<0.01);同时,AC3-I组Ito电流密度显著高于其他三组(P<0.01),而其他三组间无明显差异。上述结果提示:转基因联合抑制Ca MKII和Ik1可使Ca MKII抑制的小鼠Ik1下调,在基础状态下不影响心脏的结构和功能变化,在注射异丙基肾上腺素后心律失常的发生亦无明显差别。本结果为进一步探讨联合抑制Ca MKII与Ik1在各种心脏疾病状态下能否更有效地拮抗心肌的不利重构打下了基础。
