Functional variation of the transthyretin gene among human populations and its correlation with amyloidosis phenotypes. (December 2013)

• Record Type: Journal Article
• Authors: Polimanti, Renato; Di Girolamo, Marco; Manfellotto, Dario; Fuciarelli, Maria
• Is Part Of: Amyloid. Volume 20:Number 4(2013:Dec.)
• Page Start: 256
• Page End: 262
• Publication Date: 2013-12
• Subjects: Amyloidosis -- Periodicals; 616.3995
• DOI: 10.3109/13506129.2013.844689
• Languages: English
• ISSNs: 1350-6129

Abstract

<abstract> <title>Abstract</title> <p> <italic>Introduction</italic>: Heterogeneity in the genotype–phenotype correlation of transthyretin (TTR)-related amyloidosis has been reported, suggesting that other factors may interact with disease-causing mutations. Additional genetic variants in the <italic>TTR</italic> gene and its surrounding regions may influence disease phenotype. To explore this hypothesis, we analyzed the <italic>TTR</italic> variation among human populations to identify functional inter-ethnic differences that could influence the TTR-related amyloidosis.</p> <p> <italic>Methods</italic>: Using the 1000 Genomes Project database, we analyzed a 20 kb region in 1092 apparently healthy individuals who belonged to 14 human populations. <italic>In silico</italic> analyses were performed to determine the functional impact of genetic variants.</p> <p> <italic>Results</italic>: These analyses showed that significant ethnic differences are present in the <italic>TTR</italic> gene, and some differences may affect <italic>TTR</italic> gene function. Specifically, the non-coding variants potentially associated with regulatory function showed a significant diversity between African and non-African individuals.</p> <p> <italic>Discussion and conclusions</italic>: Our results highlighted that cis-regulatory variants may contribute to the cardiac TTR-related amyloidosis observed in patients carrier of Val122Ile mutation, the most common in population with African origin. Indeed, non-coding variants differentiated in Africans are, in some cases, located in binding sites of transcription factors involved in cardiac development and function (i.e. E2F3_2, REST, and TEAD).</p> </abstract>