Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans
Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans
复制标题
DOI：
10.1056/nejm199702133360703
复制
发表时间：
1997-02-13
影响因子：
158.5
通讯作者：
Buxbaum, JN
中科院分区：
文献类型：
--
作者：
Jacobson, DR;Pastore, RD;Buxbaum, JN
在美国，60岁以后，孤立性心脏淀粉样变性在黑人中的发病率是白人的4倍; 3.9%的黑人是正常血清载体蛋白甲状腺素运载蛋白的淀粉样变等位基因杂合子，其中异亮氨酸取代了122位的缬氨酸（Ile 122）。我们假设，甲状腺素运载蛋白122的高患病率至少是部分负责老年性心脏淀粉样变性的频率增加之间blacks.Methods石蜡块的心脏组织，从早期的研究中获得的52,370尸体在洛杉矶，并进行了免疫组化和DNA分析。样本来自60岁以上的55名黑人中的32名和78名白人中的20名，并来自两个对照组（228例）。结果在32名黑人患者的31份心脏组织样本和20名白色患者的19份心脏组织样本中鉴定出甲状腺素运载蛋白淀粉样变性。来自黑人患者的26个可分析DNA样本中的6个（23%）和来自白色患者的19个样本中没有一个是lie 122变异体杂合的，来自同一机构的第二个、更近的、年龄匹配的无淀粉样变性黑人队列的尸检125个DNA样本中的4个（3.2%）是甲状腺素运载蛋白lie 122等位基因杂合的。在复查中，这四名患者的心脏组织含有少量的淀粉样蛋白，在最初的尸检中没有检测到。所有受试者的谎言122变异心室amyloid.Conclusions老年黑人不明原因的心脏病患者的评估应包括考虑甲状腺素运载蛋白淀粉样变性，特别是与谎言122等位基因。（C）1997年，马萨诸塞州医学会。
Background After the age of 60, isolated cardiac amyloidosis is four times more common among blacks than whites in the United States; 3.9 percent of blacks are heterozygous for an amyloidogenic allele of the normal serum carrier protein transthyretin in which isoleucine is substituted for valine at position 122 (Ile 122). We hypothesized that the high prevalence of transthyretin lie 122 is at least partially responsible for the increased frequency of senile cardiac amyloidosis among blacks.Methods Paraffin blocks of cardiac tissue were obtained from an earlier study of 52,370 autopsies in Los Angeles and were examined by immunohistochemical and DNA analyses. Samples were available from 32 of 55 blacks and 20 of 78 whites over 60 years of age with isolated cardiac amyloidosis and from two control groups (228 cases).Results Transthyretin amyloidosis was identified in 31 of the 32 cardiac-tissue samples from the black patients and in 19 of the 20 samples from the white patients. Six of the 26 analyzable DNA samples (23 percent) from the black patients and none of the 19 samples from the white patients were heterozygous for the lie 122 variant, Four of 125 DNA samples obtained at autopsy (3.2 percent) from a second, more recent, age-matched cohort of blacks without amyloidosis at the same institution were heterozygous for the transthyretin lie 122 allele. On reexamination the cardiac tissue from these four patients contained small amounts of amyloid not detected at the initial autopsies. All subjects with the lie 122 variant had ventricular amyloid.Conclusions The assessment of elderly black patients with unexplained heart disease should include a consideration of transthyretin amyloidosis, particularly that related to the lie 122 allele. (C)1997, Massachusetts Medical Society.