TTR Gene

The TTR gene (TTR stands for "transthyretin") is a protein-coding gene localized on chromosome 18q12.1.

The TTR gene encodes one of three prealbumins, which include alpha-1-antitrypsin, transthyretin, and orosomucoid. The encoded protein, transthyretin, is a homo-tetrameric carrier protein that transports thyroid hormones in plasma and cerebrospinal fluid. It is also involved in the transport of retinol (vitamin A) in plasma by associating with retinol-binding protein. The protein may also be involved in other intracellular processes such as proteolysis, nerve regeneration, autophagy, and glucose homeostasis (Ueda M 2022).

Mutations in this gene (>150 mutaitons are known) are associated with amyloid deposition(transthyretin amyloidosis) affecting mainly peripheral nerves or the heart, while a small percentage of gene mutations are non-amyloidogenic. The following syndromes are associated with mutations in the TTR gene:

• Oculoleptomeningeal amyloidosis
• Meningocerebrovascular amyloidosis
• Carpal tunnel syndrome.

Furthermore, the mutations are involved in the development of several diseases, including:

amyloidotic polyneuropathy

euthyroid hyperthyroxinemia

amyloidotic vitreous opacities

Cardiomyopathy: Left ventricular wall thickening greater than 12 mm may indicate transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Echocardiography as the most important diagnostic measure should therefore be performed early in suspected cases.

1. Adams D et al (2016) TTR kinetic stabilizers and TTR gene silencing: a new era in therapy for familial amyloidotic polyneuropathies. Expert Opin Pharmacother 17:791-802.
2. Kaku M et al (2019) Neuropathy associated with systemic amyloidosis. Semin Neurol 39: 578-588.
3. Ueda M (2022) Transthyretin: Its function and amyloid formation. Neurochem Int 155:105313.