摘要
第一部分:扩张型心肌病合并心律失常分析及机制的探讨
目的:了解扩张型心肌病(DCM)伴随心律失常的情况,探讨其相互关系及发生机制。研究背景:DCM可伴发多种心律失常,目前研究发现心律失常与DCM的关系非常密切,但国内尚无大样本分析扩心病伴发各种心律失常的具体分析。方法:649例DCM患者均行常规心电图、24h动态心电图检查及心脏超声检查,对DCM患者进行心律失常分析。结果:DCM伴随心律失常的发生率分别为:伴随一度房室阻滞54例(8.3%),高度房室阻滞21例(3.2%),左束支阻滞124例(19.1%),右束支阻滞48例(7.4%),除外束支阻滞的室内传导延迟或阻滞11例(1.6%),心房颤动188例(28.9%),不典型房扑28例(4.3%),房速与窦速36例(5.5%),病态窦房结综合征7例(1%),室早与室速419例(64.5%),预激综合征4例(0.6%)。房颤与不典型房扑组(共188例)左房左右横径(LA)为44.1±10.6mm,同无房颤、房扑组(37.5±10.8)比较有明显差异(P＜0.05),室早与室速组LVED69.7±11.2mm,同无室早和室速组相比(LVED66.9±13mm)无明显差异(P＞0.5)。高度房室阻滞、左束支与右束支阻滞及室内阻滞组LVED为70.3±14.3mm,与无房室阻滞和束支阻滞及室内阻滞组(LVED65.8±10.2mm)相比有明显差异,P＜0.05。结论:多数DCM患者同时伴随明显心律失常,其中以室早与室速最常见,可能与DCM猝死相关密切;房颤、房扑组与不伴房颤和房扑组心房左右径相比有显著差异,房室阻滞、束支阻滞组与无此种心律失常的DCM组LVED有明显差异。考虑房颤、不典型房扑及房室阻滞和束支阻滞与心脏结构明显改变有关。
第二部分:扩张性心肌病患者钠离子通道SCN5A基因单核苷酸多态性研究
近期研究新发现了钠离子通道基因SCN5A突变是扩张型心肌病(DCM)的一种分子机制,进一步揭示心力衰竭的病因机制中,离子失平衡为一种重要的发病机制,但对于SCN5A的单核苷酸多态性(single nucleotide polymorphism,SNP)与扩张型心肌病的相关性未见报道,鉴于SNP存在种族上的差异,我们对5个已发现的多态位点在中国汉族人群分布及与DCM之间的相关性进行研究。选择对基因的表达具有重要功能的外显子1和其上游的调控区及下游外显子内含子交界区序列通过直接测序法进行SNP筛查,并进一步分析多态位点与扩张型心肌病的关联性。
材料和方法:连续选取2003年10月至2006年12月在北京阜外心血管病医院心内科住院及部分急诊的汉族患者,排除合并肥厚性心肌病、先天性心脏病、瓣膜性心脏病、甲状腺功能亢进或减低,确诊为DCM的患者共计362例,男性276例,女性86例。选取自2003-2006年在北京市石景山区某社区体检人群18岁以上并且高血压及糖尿病的比例与病例组相匹配者634例作为正常对照组。对于SCN5A基因的H558R、P1090L、4299+53T＞C、C 5457T(D1819D)及V1950L多态位点的基因型鉴定采用限制性片段长度多态性分析(RFLP)。并随机选取病例及对照组中的各30例,采用直接测序的方法进行SNP筛查,并选择等位基因频率较高的-941G/A、-509A/C多态位点进行病例对照分析,基因型鉴定方法同上。x~2检验用于单因素分析时检验多态与DCM间的关联,多元非条件Logistic回归模型用于检验多态位点与疾病的独立关联及与环境因素的交互作用。
SCN5A基因多态性研究结果:1)SCN5A H558R、P1090L、4299+53T＞C、C5457T(D1819D)及V1950L在中国汉族人群中的少见等位基因频率分别为11.1%、5.2%、28.2%、31.8%及0.4%。此研究中的前4个位点多态性频率均＞1%,可归为多态位点,V1950L的多态性频率＜1%,不能归为多态位点。2)对5个SNP位点在病例组与对照组间出现频率进行单变量分析,P1090L等位基因频率两组间差别显著,P=0.008,显示与DCM的相关性明显。4299+53T＞C基因型频率两组间差别显著,P=0.037,可能与DCM易感性相关。
结论:中国汉族人群中SCN5A基因中,P1090L等位基因频率及4299+53T＞C的多态性与DCM易感性可能有关,其在DCM发病机制中的作用有待进一步进行功能研究。
Objective: The purpose of this work is to analyze the types of arrhythmia and the relationship with the cardiac structure in patients with idiopathic dilated cardiomyopathy (DCM). Background: DCM has a close relationship with arrhythmia. Arrhythmia in patients with DCM is still an open issue in large sample. Method: The data of electrocardiogram, Holter, and Ultrasonic Cardiogram (UCG) of 649 patients with DCM was studied. Results: The types of arrhythmia accompany with DCM include: 54 (8.3%) patients sufferring from I°atria-ventricular block(AVB) , 21(3.2%) cases with severe AVB, 124(19.1%) cases with left branch block(LBBB), 48(7.4%) with right branch block(RBBB), 11(1.6%) with intraventricular block, 188(28.9%) with atrial fibrillation(Af), 28(4.3%) with untypical atrial flutter, and 36(5.5%)with paroxysm atrial tarchycardia(AT) or sinus tarchycardia, 7(1%) with sick sinus node syndrome, 419(64.5%) with preventricular contracts (PVc) and ventricular tarchycardia(VT), 4(0.6%) with W-P-W syndrome. The left atria diameter of the group with Af (28.9%) is 44.1±10.6mm, and is different from the group without Af (P<0.05). Left ventricular end diastolic diameter (LVED) of the cases with severe AVB, LBBB, RBBB, and intraventricular block is 70.3±14.3mm, and is different obviously from the LVED in the opposie group (65.8±10.2mm, P<0.05). Conclusions: In groups of patients with DCM, occurrence of major arrhythmic events is very often, especially ventricular arrhythmia. The ventricular arrhythmia might improve the risk of sudden arrest in these patients. Occurrence of Af and myocyte conduct block is related with the structure of the heart.
Abjective: The mutation of SCN5A gene which encodes I_(Na) might lead to Dialated Cardiomyopathy (DCM) according to some studies, but the relationship of SCN5A single nucleotide polymorphism (SNP) and DCM has not been reported. As the difference of SNP exists in different population, the association of five SCN5A polymorphisms and DCM in Adult Chinese Han population will be studied and analyze the association between SNPs discovered and DCM. Methods: A case-control design was applied in this study. A total of 362 unrelated hospitalized patients (Male:276 cases, Female: 86 cases) diagnosed DCM were enrolled from Fuwai Hospital between Oct 2003 and Dec 2004. At the same time, control subjects of total 634 cases (Male: 510 cases, Female: 124) were recruited from individuals participating in a community-based survey. First, five SNPs of SCN5A gene H558R, P1090L, 4299+53T>C, C 5457T (D1819D) and V1950L were genotyped by restriction fragment length polymorphism (RFLP) in all subjects. Multivariate analysis was performed to investigate the independent effect or interaction between the polymorphisms and DCM. Statistical analysis was conducted using the SSPS 11.5 version for Windows. Result: 1) Minor allele frequencies of H558R, P1090L, 4299+53T>C, C5457T (D1819D) and V1950L were 11.1%, 5.2%, 28.2%, 31.8% and 0.4%. V1950L was not considered as polymorphism because of frequency less than 1%. 2) The frequency of the allele P1090L (P=0.008) and the polymorphism of 4299+53T>C between the DCM group and the control one is different obviously (P=0.0373). Conclusion: The study suggested the allele of P1090L and 4299+53T>C polymorphisms of SCN5A gene might be related to DCM.
引文
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