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. 2024 Jun;31(2):124-131.
doi: 10.1080/13506129.2024.2322479. Epub 2024 Mar 6.

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

Nicholas S Hendren  1   2 , James A De Lemos  1   2 , Jarett D Berry  3 , Julia Kozlitina  4 , Lorena Saelices  5 , Alan X Ji  6 , Zhili Shao  7 , Chia-Feng Liu  7 , Sonia Garg  1   2 , Maryjane A Farr  1   2 , Mark H Drazner  1   2 , W H Wilson Tang  7   8 , Justin L Grodin  1   2
Affiliations

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

Nicholas S Hendren et al. Amyloid. 2024 Jun.

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.

Keywords: Retinol binding protein 4; V122I carriers; hereditary amyloidosis; prealbumin; transthyretin amyloidosis.

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Conflict of interest statement

Conflict of Interest: NSH report no relevant conflicts of interest or disclosures. JAd reports grant support from Roche Diagnostics and Abbott Diagnostics, and consulting fees from Beckman Coulter, Bayer Health Care Diagnostics, Astra Zeneca, Johnson and Johnson, Pfizer and Regeneron. JLG reports consulting fees from Pfizer, Eidos/BridgeBio, Alnylam, Astra-Zeneca, and Sarepta.

Figures

Figure 1.
Figure 1.. Circulating TTR and RBP4 levels by V122I carrier status in DHS-1 and DHS-2
A - TTR levels by TTR V122I carrier status in DHS-1. B – TTR levels by TTR V122I carrier status in DHS-2. C – RBP4 levels by TTR V122I carrier status in DHS-2. Abbreviations: DHS-1, Dallas Heart Study 1; DHS-2, Dallas Heart Study 2; RBP4, retinol binding protein 4; TTR, Transthyretin.
Figure 2.
Figure 2.. Correlation between circulating TTR and RBP4 levels in individuals with V122I TTR carriers, T119M TTR carriers, and non-carrier controls
Abbreviations: RBP4, retinol binding protein 4; TTR, Transthyretin.
See this image and copyright information in PMC

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