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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)


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-N/A
JournalBMC Genomics
Publication statusPublished - 2017
Externally publishedYes


  • Amyloid
  • Amyloidosis
  • Biotechnology
  • Gene Expression Regulation
  • Gene expression
  • Genetics
  • Genotype
  • Genotype-phenotype correlation
  • Humans
  • Mutation
  • Phenotype
  • Prealbumin
  • Transthyretin


Dive into the research topics of 'Population diversity of the genetically determined TTR expression in human tissues and its implications in TTR amyloidosis'. Together they form a unique fingerprint.

Cite this