Retinol Binding Protein 4 as a Screening Biomarker for Hereditary TTR Amyloidosis in African American Adults With TTR V142I.
Retinol Binding Protein 4 as a Screening Biomarker for Hereditary TTR Amyloidosis in African American Adults With TTR V142I.
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视黄醇结合蛋白4作为TTR V142I的非裔美国人成年人的遗传性TTR淀粉样变性的筛查生物标志物。
DOI：
10.1016/j.cardfail.2021.05.009
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发表时间：
2021-09
影响因子：
6
通讯作者：
Abul-Husn NS
中科院分区：
文献类型：
--
作者：
Kontorovich AR;Abul-Husn NS
与遗传性甲状腺素运载蛋白淀粉样变性（hATTR）相关的TTR V142 I变体（以前称为V122 I）是全球最常见的TTR变体，最近的患病率估计为1/330（1）。在美国，高达4%的非洲裔美国人（AA）为V142 I杂合子（即V142 I+）（2），这被认为部分解释了60岁以上AA患者中心脏淀粉样变性（CA）的发生率是欧洲血统患者的4倍（3）。hATTR的非心脏临床特征，如腕管综合征、椎管狭窄和多发性神经病（“红旗”）可先于CA数年，并且已在未诊断的V142 I+个体中观察到，这些个体没有心力衰竭（HF）症状（4）。然而，V142 I+个体中hATTR的临床诊断通常仅在他们发展明显的CA和HF后进行。视黄醇结合蛋白4（RBP 4）是脂质运载蛋白视黄醇载体，其与血清中的甲状腺素运载蛋白1：1结合，作为内源性甲状腺素运载蛋白稳定剂起作用（5）。循环RBP 4水平取决于RBP 4和甲状腺素运载蛋白的相互作用，并且在hATTR中降低。当与其他临床参数结合时，已证明RBP 4水平可区分60岁或60岁以上AA患者中的V142 I CA和非CA HF（6）。然而，RBP 4尚未在未确诊或年轻的V142 I+个体中进行研究，以告知临床前hATTR。在这里，我们假设RBP 4水平将区分没有明显CA的年轻未诊断V142 I+个体与V142 I-个体，表明循环不稳定的甲状腺素运载蛋白，并可能使hATTR的早期风险预测成为可能。
The TTR V142I variant (previously known as V122I), associated with hereditary transthyretin amyloidosis (hATTR), is the most common TTR variant worldwide, with recent prevalence estimates of 1 in 330 individuals (1). Up to 4% of African American (AAs) in the US are heterozygous for V142I (ie, V142I+)(2), which, in part, is thought to explain the observation that cardiac amyloidosis (CA) is four times more common among AA than European descent patients over 60 years of age (3).. Non-cardiac clinical features of hATTR such as carpal tunnel syndrome, spinal stenosis and polyneuropathy (“red flags”) can precede CA by several years, and have been observed in undiagnosed V142I+ individuals absent heart failure (HF) symptoms (4). Nevertheless, the clinical diagnosis of hATTR in V142I+ individuals is typically only made after they develop overt CA and HF.Retinol binding protein 4 (RBP4) is a lipocalin retinol carrier that binds 1: 1 with transthyretin in serum, functioning as an endogenous transthyretin stabilizer (5). Circulating RBP4 levels depend on the interaction of RBP4 and transthyretin, and are reduced in hATTR. RBP4 levels have been shown to discriminate between V142I CA and non-CA HF in AA patients 60 years or older when integrated with other clinical parameters (6). However, RBP4 has not been studied in undiagnosed or younger V142I+ individuals without CA to inform preclinical hATTR. Here, we hypothesized that RBP4 levels would differentiate younger undiagnosed V142I+ individuals without overt CA from V142I-individuals, indicating circulating destabilized transthyretin and potentially enabling earlier risk prediction for hATTR.
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影响因子：
120.7
作者：
Damrauer, Scott M.;Chaudhary, Kumardeep;Do, Ron
通讯作者：
Do, Ron
影响因子：
--
作者：
Soper ER;Suckiel SA;Braganza GT;Kontorovich AR;Kenny EE;Abul-Husn NS
通讯作者：
Abul-Husn NS
影响因子：
24
作者：
Arvanitis M;Koch CM;Chan GG;Torres-Arancivia C;LaValley MP;Jacobson DR;Berk JL;Connors LH;Ruberg FL
通讯作者：
Ruberg FL
影响因子：
158.5
作者：
Jacobson, DR;Pastore, RD;Buxbaum, JN
通讯作者：
Buxbaum, JN
影响因子：
56.9
作者：
MONACO, HL;RIZZI, M;CODA, A
通讯作者：
CODA, A