Circulating transthyretin and retinol binding protein 4 levels among middle-age V122I TTR carriers in the general population.

IF 5.2 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-06-01 Epub Date: 2024-03-06 DOI:10.1080/13506129.2024.2322479

Nicholas S Hendren, James A De Lemos, Jarett D Berry, Julia Kozlitina, Lorena Saelices, Alan X Ji, Zhili Shao, Chia-Feng Liu, Sonia Garg, Maryjane A Farr, Mark H Drazner, W H Wilson Tang, Justin L Grodin

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引用次数: 0

Abstract

Background: Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has a long latency phase before clinical onset, creating a need to identify subclinical disease. We hypothesized circulating transthyretin (TTR) and retinol binding protein 4 (RBP4) levels would be associated with TTR carrier status and correlated with possible evidence of subclinical ATTRv-CA.

Methods: TTR and RBP4 were measured in blood samples from V122I TTR carriers and age-, sex- and race-matched non-carrier controls (1:2 matching) among Dallas Heart Study participants (phases 1 (DHS-1) and 2 (DHS-2)). Multivariable linear regression models determined factors associated with TTR and RBP4.

Results: There were 40 V122I TTR carriers in DHS-1 and 54 V122I TTR carriers in DHS-2. In DHS-1 and DHS-2, TTR was lower in V122I TTR carriers (p < .001 for both), and RBP4 in DHS-2 was lower in V122I TTR carriers than non-carriers (p = .002). Among V122I TTR carriers, TTR was negatively correlated with markers of kidney function, and limb lead voltage (p < .05 for both) and TTR and RBP4 were correlated with atrial volume in DHS-2 (p < .05).

Conclusions: V122I TTR carrier status is independently associated with lower TTR and RBP4 in comparison with non-carriers. These findings support the hypothesis that TTR and RBP4 may correlate with evidence of subclinical ATTRv-CA.

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普通人群中 V122I TTR 中年携带者的循环转甲状腺素和视黄醇结合蛋白 4 水平。

背景：遗传性转甲状腺素心脏淀粉样变性（ATTRv-CA）在临床发病前有很长的潜伏期，因此需要识别亚临床疾病。我们假设循环中的转甲状腺素（TTR）和视黄醇结合蛋白 4（RBP4）水平与 TTR 携带者状态有关，并与亚临床 ATTRv-CA 的可能证据相关：在达拉斯心脏研究参与者（第一阶段（DHS-1）和第二阶段（DHS-2））中，对 V122I TTR 携带者和年龄、性别及种族匹配的非携带者对照组（1:2 匹配）的血液样本中的 TTR 和 RBP4 进行了测量。多变量线性回归模型确定了与 TTR 和 RBP4 相关的因素：结果：DHS-1 中有 40 名 V122I TTR 携带者，DHS-2 中有 54 名 V122I TTR 携带者。在 DHS-1 和 DHS-2 中，V122I TTR 携带者（p TTR 携带者）的 TTR 低于非携带者（p = .002）。在 V122I TTR 携带者中，TTR 与肾功能指标和肢体导联电压呈负相关（p p 结论）：与非携带者相比，V122I TTR 携带者身份与较低的 TTR 和 RBP4 独立相关。这些发现支持 TTR 和 RBP4 可能与亚临床 ATTRv-CA 的证据相关的假设。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Amyloid-Journal of Protein Folding Disorders 生物-生化与分子生物学

CiteScore

10.60

自引率

10.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Amyloid: the Journal of Protein Folding Disorders is dedicated to the study of all aspects of the protein groups and associated disorders that are classified as the amyloidoses as well as other disorders associated with abnormal protein folding. The journals major focus points are: etiology, pathogenesis, histopathology, chemical structure, nature of fibrillogenesis; whilst also publishing papers on the basic and chemical genetic aspects of many of these disorders. Amyloid is recognised as one of the leading publications on amyloid protein classifications and the associated disorders, as well as clinical studies on all aspects of amyloid related neurodegenerative diseases and major clinical studies on inherited amyloidosis, especially those related to transthyretin. The Journal also publishes book reviews, meeting reports, editorials, thesis abstracts, review articles and symposia in the various areas listed above.