Population diversity of the genetically determined TTR expression in human tissues and its implications in TTR amyloidosis

Andrea Iorio, Flavio De Angelis, Marco Di Girolamo, Marco Luigetti, Luca G Pradotto, Anna Mazzeo, Sabrina Frusconi, Filomena My, Dario Manfellotto, Maria Fuciarelli, Renato Polimanti

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Transthyretin (TTR) amyloidosis is a hereditary disease with a complex genotype-phenotype correlation. We conducted a literature survey to define the clinical landscape of TTR amyloidosis across populations worldwide. Then, we investigated whether the genetically determined TTR expression differs among human populations, contributing to the differences observed in patients. Polygenic scores for genetically determined TTR expression in 14 clinically relevant tissues were constructed using data from the GTEx (Genotype-Tissue Expression) project and tested in the samples from the 1,000 Genomes Project.

RESULTS: We observed differences among the ancestral groups and, to a lesser extent, among the investigated populations within the ancestry groups. Scandinavian populations differed in their genetically determined TTR expression of skeletal muscle tissue with respect to Southern Europeans (p = 6.79*10-6). This is in line with epidemiological data related to Swedish and Portuguese TTR Val30Met endemic areas. Familial amyloidotic cardiomyopathy (TTR deposits occur primarily in heart tissues) presents clinical variability among human populations, a finding that agrees with the among-ancestry diversity of genetically determined TTR expression in heart tissues (i.e., Atrial Appendage p = 4.55*10-28; Left Ventricle p = 6.54*10-35).

CONCLUSIONS: Genetically determined TTR expression varied across human populations. This might contribute to the genotype-phenotype correlation of TTR amyloidosis.

Original languageEnglish
Pages (from-to)254
JournalBMC Genomics
Issue number1
Publication statusPublished - Mar 23 2017


  • Amyloidosis
  • Gene Expression Regulation
  • Genotype
  • Humans
  • Phenotype
  • Prealbumin
  • Journal Article
  • Research Support, Non-U.S. Gov't


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