扩张型心肌病与MHC-DQ基因多态性的关联分析

目的　探讨扩张型心肌病 ( DCM)易感的分子机制和确立一种较为实用的 MHC- 类基因的检测方法。方法　采用聚合酶链式反应和顺序特异性引物 ( PCR- SSP)基因分析方法 ,对 31例扩张型心肌病患者及 30例无血缘关系的健康人的人类主要组织相容性复合体 ( MHC- 类 ) DQ各等位基因及亚基因进行了检测分析 ,并将该方法与其它检测 MHC- 类基因的方法进行对比。结果　结果表明 ,MHC- DQB1* 0 30 1基因与 DCM呈正相关 ( P <0 .0 1) ,其它 MHC- DQB1*其它各等位基因未见异常。结论　 MHC- DQB1* 0 30 1基因可能为北方汉族人 DCM的致病易感基因。尽管目前 MHC- 类基因分型方法已有多种 ,但所采用的方法 ( PCR- SSP)具有快速、简便、敏感、准确和可靠等优点。     

扩张型心肌病HLA－DRB_1基因多态性的研究

借助聚合酶链反应（ＰＣＲ）／序列特异性引物（ＳＳＰ）技术对４２例扩张型心肌病（ＤＣＭ）患者和１６８例正常对照者进行人类白细胞抗原（ＨＬＡ）－ＤＲＢ１基因型分析。结果发现ＤＣＭ组ＨＬＡ－ＤＲＢ１＊１１基因频率与对照组比较明显增高（２６．１９％对１３．１％，Ｐ＜０．０５），其ＲＲ＝２．３６。其他等位基因频率在ＤＣＭ组与对照组间差异无显著性。提示ＨＬＡ－ＤＲＢ１＊１１基因可能与ＤＣＭ有关联。     

中国北方汉族人群人类白细胞抗原-DQA1及-DQB1基因第二外显子多态性与扩张型心肌病遗传易感性研究

目的:研究人类白细胞抗原(human leukocyte antigen,HLA)-DQA1,HLA-DQB1基因第二外显子多态性与我国北方汉族人群特发性扩张型心肌病(idiopathic dilated cardiomyopathy,IDC)的相关性及连锁关系。探讨特发性扩张型心肌病发病的免疫学机制及遗传易感性。 方法:采用聚合酶链反应-序列特异性引物法对68例特发性扩张型心肌病患者和15例特发性扩张型心肌病家系成员(n=83,IDC组)及100名健康个体(正常对照组)行HLA-DQA1,HLA-DQB1第二外显子基因分型;IDC组均接受超声心动图检测射血分数并据此分层:射血分数0.35-0.5者(n=21),射血分数0.15-0.34者(n=36)及<0.15者(n=26)。 结果:HLA-DQA1*0501基因和HLA-DQB1*0303基因频率在IDC组明显高于正常对照组。且该趋势随射血分数降低而愈趋明显,表现为HLA-DQA1*0501及HLA-DQB1*0303基因型在射血分数<0.15(阳性基因数分别为41和21)的特发性扩张型心肌病患者中分布高于射血分数≥0.15(阳性基因数分别为27和15)者。IDC组HLA-DQA1*0201基因频率和HLA-DQB1*0502、*0504基因频率明显低于正常对照组(P<0.05)。HLA-DQA1,HLA-DQB1基因与特发性扩张型心肌病家系连锁分析Lod值<1。 结论:HLA-DQA1*0501和HLA-DQB1*0303与我国北方汉族特发性扩张型心肌病患者遗传易感性相关;而HLA-DQA1*     

扩张型心肌病与MHC-DR基因多态性的关联

扩张型心肌病 (DCM) ,是一种严重的心脏疾病 ,迄今为止 ,DCM的病因及发病机理仍不十分清楚 ,众多研究发现 ,DCM也具有遗传家族史等倾向 ,其发病与免疫失衡有关。人类免疫遗传基因位于MHC区域内 ,人们从免疫遗传学角度对该病进行研究 ,发现DCM与人类的免疫遗传基因 (MHC Ⅱ )的多态性有关。尤其是与MHC Ⅱ类基因的DR关系密切。新近研究表明MHC DR抗原在DNA序列上还存在着高度多态性[1]。为了分析中国汉族人MHC Ⅱ类基因在DCM病发生发展中的作用机制 ,为该病的诊断 ,治疗和预防提供依据 ,也使基因分型早日代替血清学分型 ,我们…     

心电图对特发性扩张型心肌病的短期预后分析

我们对1996年1月至1998年12月收治的53例扩张型心肌病(IDC)患者的心电图(ECG)改变进行了分析,旨在了解IDC短期预后及死亡方式,现报告如下。1　临床资料本组男27例,女26例;年龄30～70岁,平均57.3±11.6岁;病程3～11年。IDC诊断均符合1980年WHO制订的标准,左室舒张末期内径(LVEDd)≥55mm;多普勒超声心动图示左室整体收缩功能减弱(短径缩短率<30%)。患者临床表现为胸闷、心悸、呼吸困难、下肢浮肿、胸腹水等,属Brandenburg[1]病程分段中第三阶段(晚期)。2　检查方法本组病例住院后记录12导联ECG2次,按国际标准方法行彩色多普勒超声心…     

氯沙坦治疗特发性扩张型心肌病疗效观察

本研究采用氯沙坦并β受体阻滞剂治疗特发性扩张型心肌病(IDCM),观察其对心脏重塑的效应。1.资料与方法:1997年1月到2002年12月,本院收治的56例:IDCM住院患者,男性30例,女性26例,年龄(48±15)岁,经超声心动图检查,符合WHO诊断IDCM的标准。随机分为两组:常规治疗组26例,男性14例,女性12例,年     

徐州地区汉族人及慢性乙型肝炎HLA-A基因多态性的研究

探讨慢性乙型肝炎与HLA-A位点的等位基因多态性.用PCR-SSP方法对徐州地区汉族正常组和慢性乙型肝炎组的HLA-A基因多态性进行分析.HLA-A＊0201-17出现的频率在慢性乙型肝炎组为45.57%,高于正常组的29.69%,P=0.002＜0.05,RR=1.983,（95%CI：1.227-3.080）,具有统计学意义.HLA-A＊0201-17与慢性乙型肝炎较高的相关性,可能为易感基因.     

ZASP基因与特发性扩张型心肌病相关性研究

目的 探讨成都地区特发性扩张型心肌病(IDCM)人群中是否存在z带选择性缝接PDZ基序蛋白(ZASP)基因突变以及与该地区IDCM患者的相关性.方法 2006年1月至2007年12月在四川大学华西医院采用聚合酶链反应-单链构象多态性技术(PCR-SSCP)结合DNA测序方法,筛检成都地区无血缘关系汉族人群(包括120例IDCM患者,100名健康对照者)ZASP基因外显子4、6、10的可能突变位点.结果 在IDCM组和正常对照组中,ZASP基因外显子4、6单链构象多态性(SSCP)电泳图谱未发现差异;但外显子10 SSCP电泳图谱发现差异,经DNA测序证实为G216T杂合子与T216T纯合子.G216T杂合子在IDCM组检出28例,对照组检出12例;T216T纯合子在IDCM组检出9例,对照组检出4例.G/T基因型及T等位基因频率在IDCM组和对照组中差异有统计学意义(P<0.05).结论 ZASP基因外显子10 G216-T多态性与成都地区汉族IDCM患者遗传易感性相关;提示T等位基因为扩张型心肌病的易感基因.     

扩张型心肌病与HLA-B*基因的多态性关系

目的探讨北方汉族人扩张型心肌病(dilated cardiomyopathy,DCM)遗传易感性与人类主要组织相容性复合体(HLA-B*)基因多态性的关系。方法采用聚合酶链反应和顺序特异性引物(PCR-SSP)基因多态性分析方法,对31例扩张型心肌病患者及29例无血缘关系健康人的HLA-B*各等位基因及亚基因进行检测分析。结果HLA-B*35基因与DCM呈正相关(相对危险度RR=3．9375,P<0．05),其他HLA-B*各等位基因未见异常,差异均无统计学意义(P>0．05)。结论HLA-B*35基因可能是北方地区汉族人DCM的致病易感基因之一,为揭示DCM的发病机制中免疫遗传学所起的作用提供了重要信息和依据。     

人类白细胞抗原DRB1基因与肺结核的相关性研究

目的探讨HLA-DRB1基因多态性与肺结核(PTB)的遗传关联性及其与临床表现的关系。方法采用聚合酶链反应-序列特异性引物(PCR-SSP)方法,对74例PTB患者及90名正常人的HLA-DRB1等位基因进行分型。结果与对照组相比,PTB病例组的DRB1*15等位基因频率显著增高(34.3%比17.0%,Pc<0.05,RR=2.91),HLA-DRB1*12基因频率高(15.4%比7.5%),但统计学上无显著性差异(Pc>0.05);而DRB1*11基因频率显著低于对照组(1.4%比9.9%,Pc<0.05,RR=0.12)。HLA-DRB1*15阳性患者中复治病例数和耐药病例数均显著高于HLA-DRB1*15阴性组(P<0.05)。结论HLA-DRB1*15可能是PTB的易感基因,DRB1*11可能为保护基因,HLA-DRB1*15基因与PTB临床特征有一定相关性。     

Haemochromatosis gene mutations in idiopathic dilated cardiomyopathy

BACKGROUND—Two common mutations of the haemochromatosis associated gene (HFE) (cys282tyr (C282Y) and his63asp (H63D)) have been implicated in haemochromatosis and as modulators in cardiovascular disease.
OBJECTIVE—To investigate the role of these mutations in the pathogenesis of idiopathic dilated cardiomyopathy.
DESIGN AND SETTING—Case-control and prospective cohort study of patients attending a cardiomyopathy unit in a tertiary referral cardiac centre.
METHODS—207 unrelated white patients with dilated cardiomyopathy, followed up for 259 patient years, and 200 controls were tested for HFE C282Y and H63D mutations by polymerase chain reaction and restriction digestion.
RESULTS—31/207 patients (15%) v 24/200 controls (12%) carried C282Y (adjusted odds ratio (OR) 1.2 (95% confidence interval 0.7 to 2.2)), 74/207 (36%) v 53/200 (27%) carried H63D (OR 1.6 (1.1 to 2.5)), and 10/207 (4.8%) v 4/200 (2%) were compound heterozygotes (OR 2.6 (0.8 to 8.5)). Four patients and six controls were H63D homozygous and one was C282Y homozygous. There was a progressive increase in mean serum iron ([Fe]) and transferrin saturations from patients with no mutation ([Fe] = 16.3 µmol/l, transferrin saturation = 23.7%) through H63D heterozygotes (17.5 µmol/l, 25.8%), C282Y heterozygotes (17.1 µmol/l, 26.6%), H63D homozygotes (20.0 µmol/l, 33.5%), compound heterozygotes (26.8 µmol/l, 41.7%), and C282Y homozygotes (34 µmol/l, 71%). At follow up (median 90 months) the rate of death or cardiac transplantation was 52/207 (25%). C282Y heterozygotes had less ventricular dilatation (mean (SD): 59.9 (1.7) mm v 64.9 (0.9) mm, p < 0.05), better fractional shortening (24 (1.7)% v 18.8 (1.4)%, p < 0.01), and a trend towards improved survival without transplantation. [Fe] and transferrin saturation did not correlate with disease severity and were not associated with reduced survival.
CONCLUSIONS—The frequency of the H63D mutation is significantly increased in patients with idiopathic dilated cardiomyopathy. As H63D has a relatively minor effect on iron status, the mechanism of this association may be unrelated to iron metabolism.


Keywords: dilated cardiomyopathy; genetics; haemochromatosis     

Natriuretic peptides in patients with diastolic dysfunction due to idiopathic dilated cardiomyopathy.

AIMS: The degree of systolic dysfunction does not always correlate with functional impairment in patients with congestive heart failure. In contrast, diastolic dysfunction correlates well with functional impairment. In heart failure, both elevation of N-terminal proatrial natriuretic peptide and B-type natriuretic peptide are markers of a poor prognosis.METHODS: We investigated 32 patients (26 male, 6 female; mean age 55+/-2 years) with dilated cardiomyopathy and sinus rhythm. M-mode echocardiography and 2D-echocardiography were carried out in each patient. Pulsed-wave Doppler inflow signals were obtained and the following parameters were measured: maximal E wave and maximal A wave velocity, E/A ratio, E wave deceleration time, A wave deceleration time. Immediately after echocardiography blood samples were collected from patients in the supine position. N-terminal proANP and brain natriuretic peptide were measured using a radioimmuno assay.RESULTS: The left ventricular ejection fraction was 34+/-1%, the left ventricular end-diastolic diameter on M-mode echocardiography was 68+/-1 mm, while left atrial diameter was 45+/-1 mm. Univariate analysis revealed a significant correlation between both left atrial diameter and ejection fraction and N-terminal proANP and brain natriuretic peptide. All transmitral Doppler parameters showed a significant correlation with N-terminal proANP and brain natriuretic peptide. On forward stepwise regression analysis, left atrial diameter and ejection fraction were able to predict both N-terminal proANP and brain natriuretic peptide. However, of the diastolic parameters only the E/A ratio remained significant. Mildly symptomatic patients differed significantly from severely symptomatic patients in all Doppler parameters. Mildly symptomatic patients had significantly lower levels of N-terminal proANP (0.571+/-0.079 vs 2.282+/-0.340 nmol. l(-1);P<0.001) and brain natriuretic peptide (51+/-14.8 vs 474.2+/- 86.8 pg. ml(-1);P<0. 001).CONCLUSION: There is a close relationship between natriuretic peptides and diastolic Doppler parameters of left ventricular filling in patients with dilated cardiomyopathy. There is also a significant difference between patients with mild and severe functional impairment regarding both natriuretic peptides and transmitral Doppler parameters.     

Shock occurrence and survival in 49 patients with idiopathic dilated cardiomyopathy and an implantable cardioverter-defibrillator

To determine shock occurrence and survival, 49 patients withidiopathic dilated cardiomyopathy presenting with cardiac arrest(82%), syncope (12%) or ventricular tachycardia without syncope(6%) were followed for 28 ±28 months after cardioverter-defibrillator(ICD) implant according to the intention to treat principle.Using the Kaplan-Meier method, the actuarial incidence for anyspontaneous shocks was 20%, 58%, and 77%, and the incidenceof appropriate shocks was 16%, 49%, and 72% at 1, 3, and 5 yearsof follow-up, respectively. Only two of 49 study patients (4%)with an active ICD died suddenly during follow-up. Another twopatients, however, with an inactive device died suddenly, resultingin a sudden death rate of 2% per year with an active ICD, and5% per year, according to the intention to treat principle.The incidence of cardiac death from any cause was 8%, 25%, and35%, and the incidence of total mortality was 14%, 39%, and49% during 1, 3, and 5 years of follow-up, respectively. Therewas no difference in the Kaplan-Meier survival curves for shockedvs non-shocked patients. Thus, in this selected patient populationwith idiopathic dilated cardiomyopathy the majority of patientsreceived ‘appropriate’ shocks during follow-up,and the sudden death rate with active ICD is low.     

Prognostic value of pharmacologic stress echocardiography in patients with idiopathic dilated cardiomyopathy: a prospective, head-to-head comparison between dipyridamole and dobutamine test

BackgroundInotropic reserve identified by dobutamine or dipyridamole stress echocardiography is associated with a better outcome in patients with idiopathic dilated cardiomyopathy (DCM), although the relative prognostic value of each remains unsettled. The purpose of the present study was to assess the relative prognostic value of dobutamine versus dipyridamole stress echocardiography for the prediction of all-cause death in patients with idiopathic DCM.Methods and ResultsEighty-seven patients (63 were male, aged 54 ± 12 years) with DCM and an ejection fraction less than 35% underwent both dipyridamole and dobutamine stress echocardiography on different days and in a random order. In all patients, wall motion score index and ejection fraction were evaluated at baseline and peak stress. All patients were followed up for an average of 52 months. All-cause death was identified as the prognostic end point. During the follow-up, 26 all-cause deaths occurred (29.8%). On multivariate analysis, either dobutamine echocardiography (relative risk 0.299; P = .02; 95% confidence interval 0.084–0.835) or dipyridamole echocardiography (relative risk 0.161; P < .00; 95% confidence interval 0.07–0.394) added significantly to a prognostic model based on clinical and resting echocardiographic variables. Survival was 83% in patients with dobutamine and 84% in patients with dipyridamole-induced contractile reserve.ConclusionsDobutamine and dipyridamole stress echocardiography have similar feasibility and prognostic accuracy in DCM risk stratification.     

环磷腺苷葡胺联合美多心安治疗扩张型心肌病184例临床分析

目的：研究环磷腺苷葡胺（心先安）与美多心安（倍他乐克）及基础治疗（洋地黄、利尿剂和血管扩张剂）对扩张型心肌病所致的心力衰竭的临床疗效。方法：对184例确诊的扩张型心肌病病人随机分为基础治疗组，倍他乐克组（在基础治疗上加倍他乐克）；心先安组（在倍他乐克组加用心先安）。观察各组临床表现及心功能的变化，结果：心先安组在对扩张型心肌病所致的心力衰竭的临床表现及各项心功能指标的改善方面均优于其他两组（P＜0．05）。结论：心先安是治疗扩型心肌病所致的心力衰竭安全而有效的药物。     

The prognostic use of serum concentrations of cardiac troponin-I,CK-MB and myoglobin in patients with idiopathic dilated cardiomyopathy

Objective

To examine the association between survival and serum concentrations of cTnI, CK-MB, and myoglobin in patients with idiopathic dilated cardiomyopathy (IDC).

Background

It has been suggested that elevated circulating biomarkers of myocardial damage such as cardiac troponin-I (cTnI), creatine kinase MB (CK-MB) and myoglobin are independent risk factors for mortality in patients with heart failure, and recent studies, although limited, showed that there was a potential association between cTnI and the prognosis of patients with dilated cardiomyopathy (DCM).

Methods

A cohort study was undertaken in 310 patients with IDC. Standard demographic information, transthoracic echocardiography, and routine blood tests were obtained shortly after hospital admission. Outcome was assessed with all-cause mortality.

Results

Among the 310 patients studied, 61 (19.7%) died during a mean follow-up of 2.2 years. There was a significant difference in the all-cause mortality rate between patients with serum cTnI >0.05 ng/mL and with cTnI ≤0.05 ng/mL (37.5% vs 15%, log-rank χ² = 18.423, P < 0.001). After adjustment for other factors associated with prognosis at baseline, serum cTnI >0.05 ng/mL, QRS duration, NYHA functional class and systolic blood pressure predicted all-cause mortality in patients with IDC. There was no association between circulating CK-MB and myoglobin levels and all-cause mortality in the studied IDC patients.

Conclusion

Serum concentrations of cTnI but not CK-MB or myoglobin are an independent predictor of all-cause mortality in patients with IDC.