Relation of clinical, echocardiographic and electrocardiographic features of cardiac amyloidosis to the presence of the transthyretin V122I allele in older African-American men.
Relation of clinical, echocardiographic and electrocardiographic features of cardiac amyloidosis to the presence of the transthyretin V122I allele in older African-American men.
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老年非洲裔美国男性心脏淀粉样变性的临床、超声心动图和心电图特征与转甲状腺素蛋白 V122I 等位基因的关系。
DOI：
10.1016/j.amjcard.2011.03.069
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Buxbaum,Joel
中科院分区：
文献类型：
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作者：
Jacobson,Daniel;Tagoe,Clement;Schwartzbard,Arthur;Shah,Alan;Koziol,James;Buxbaum,Joel
先前的研究表明，3%至4%的非洲裔美国人携带人类血清蛋白甲状腺素运载蛋白（TTR V122 I）的淀粉样蛋白等位基因。该等位基因在65岁以后出现心脏淀粉样沉积的绝对解剖学风险。在这项研究中，进行了一项病例对照比较的临床，超声心动图和心电图特征的23岁的危险携带者的淀粉样蛋白基因和46个年龄，性别和种族匹配的非携带者正在评估心脏病使用标准的临床测试。两组的血压和心脏射血分数相匹配。无受试者在研究前诊断为心脏淀粉样变性。携带淀粉样变等位基因的患者，心脏淀粉样变的超声心动图特征发生率显著高于非携带者，充血性心力衰竭和房颤的发生率也更高。观察结果表明，TTR V122 I代表了老年非裔美国男性发生临床显著心脏淀粉样变性的重大风险，表现为年龄依赖性常染色体显性疾病相关等位基因。诊断困难，但可在年龄>60岁的非裔美国人中根据年龄、舒张功能障碍的超声心动图证据和室间隔增厚进行怀疑，即使在缺乏最近可用的用于评估长轴功能和心脏磁共振成像的复杂超声心动图技术的情况下。淀粉样蛋白TTR V122 I等位基因阳性结果支持诊断，并确定了疾病的起源，这可以通过肌内膜活检来证实。
Previous studies have shown that 3% to 4% of African Americans carry an amyloidogenic allele of the human serum protein transthyretin (TTR V122I). The allele appears to have an absolute anatomic risk for cardiac amyloid deposition after 65 years of age. In this study, a case-control comparison was performed of clinical, echocardiographic, and electrocardiographic characteristics of 23 age at risk carriers of the amyloidogenic allele and 46 age-, gender-, and ethnically matched noncarriers being evaluated for cardiac disease using standard clinical testing. The 2 groups were matched for blood pressure and the cardiac ejection fraction. None of the subjects had a prestudy diagnosis of cardiac amyloidosis. Carriers of the amyloidogenic allele were found to have statistically significant increases in the occurrence of many of the echocardiographic features of cardiac amyloidosis relative to the noncarriers and a higher frequency of congestive heart failure and atrial fibrillation. The observations suggest that TTR V122I represents a substantial risk for clinically significant cardiac amyloidosis in elderly African American men, behaving as an age-dependent autosomal dominant disease-associated allele. The diagnosis is difficult to make but can be suspected in African Americans aged >60 years on the basis of age, echocardiographic evidence of diastolic dysfunction, and interventricular septal thickening, even in the absence of more recently available sophisticated echocardiographic techniques for evaluating long-axis function and cardiac magnetic resonance imaging. Positive results for the amyloidogenic TTR V122I allele support the diagnosis and define the origin of the disease, which can be confirmed by endomyocardial biopsy.