社区中单基因突变和左心室壁厚度增加:弗雷明汉心脏研究
Hiroyuki Morita1, Martin G Larson, Scott C Barr
1The Program in Genomics Applications: CardioGenomics Group--Department of Genetics, NRB Room 256, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Circulation
|June 7, 2006
概括
萨尔科默和储存基因的遗传突变在18%的社区个体中发现,左心室壁厚度 (LVWT) 无法解释的增加. 这表明遗传因素有助于LVWT异质性.
科学领域:
- 心脏病学 心脏病学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 罕见的家族性心肌病可以源于sarcomere蛋白,PRKAG2,LAMP2,alpha-galactosidase A (GLA) 和线粒体基因的突变.
- 在一般人群中,这些遗传原因导致左心室壁厚度增加 (LVWT) 的患病率仍未确定.
研究的目的:
- 调查已知心肌病相关基因对社区队列中不明原因增加的LVWT的贡献.
- 为了确定 sarcomere 蛋白和储存基因突变在增加 LVWT 的个体中的频率.
主要方法:
- 在1862年弗雷明翰心脏研究的参与者中测序了8个 sarcomere 蛋白质基因,3个存储心肌病引起的基因和27个线粒体基因.
- 鉴定了没有严重高血压或显著的大动脉疾病的不明原因增加的LVWT (最大LVWT>13毫米) 的参与者.
- 在50名符合条件的参与者中分析了基因变异,这些参与者有不明原因的LVWT增加.
主要成果:
- 在9名个体 (2名女性) 中发现了8种突变,导致不明原因的LVWT增加.
- 在五个沙科默蛋白基因 (MYH7,MYBPC3,TNNT2,TNNI3,MYL3) 中发现了七种突变.
- 检测到一个α-银酸酶A (GLA) 突变. 具有突变的个体在临床上与没有突变的个体相似.
结论:
- 大约3%的社区队列增加了LVWT,18%的这些病例与sarcomere蛋白或脂质储存基因突变有关.
- 在社区中增加LVWT是一个异质的条件.
- 各种基因中的单基因变异可能是增加LVWT的原因.
相关概念视频
Mitral Regurgitation I: Introduction
1.3K
Mitral regurgitation is characterized by the backward circulation of blood from the left ventricle to the left atrium during systole, a phase of the cardiac cycle when the heart contracts and pumps blood out of the chambers. This abnormal flow occurs primarily due to the dysfunction of the mitral valve or its supporting structures, which include the mitral leaflets, chordae tendineae, annulus, and papillary muscles.Etiology and Mechanisms:Primary Mitral Regurgitation: This type arises from...
1.3K
Mitral Stenosis I: Introduction
1.8K
Mitral Valve Stenosis (MVS) is a heart condition where the mitral valve narrows, impeding blood circulation from the left atrium to the left ventricle. The etiology and pathophysiology of this condition are multifaceted, leading to a cascade of cardiovascular complications.Causes of Mitral Valve StenosisRheumatic Heart Disease: It is the main cause of mitral valve stenosis, particularly in developing nations. This condition arises from rheumatic fever, an inflammatory illness resulting from...
1.8K
Heart Failure II: Pathophysiology
1.9K
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
1.9K
Cardiomyopathy II: Dilated Cardiomyopathy
790
Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
790
Cardiomyopathy III: Hypertrophic Cardiomyopathy
805
Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
805
Cardiomyopathy IV: Restrictive Cardiomyopathy
952
Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
952


