title: The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa.
abstract: BACKGROUND
  Transthyretin (TTR) pV142I (rs76992529-A) is one of the 113 variants in the human TTR gene associated with systemic amyloidosis. It results from a G to A transition at a CG dinucleotide in the codon for amino acid 122 of the mature protein (TTR V122I). The allele frequency is 0.0173 in African Americans.
  
  
  METHODS
  PCR-based assays to genotype 2767 DNA samples obtained from participants in genetic studies from various African populations supplemented with sequencing data from 529 samples within the 1000 Genomes Project.
  
  
  RESULTS
  The rs76992529-A variant allele was most prevalent (allele frequency 0.0253) in the contiguous West African countries of Sierra Leone, Guinea, Ivory Coast, Burkina Faso, Ghana, and Nigeria. In other African countries, the mean allele frequency was 0.011.
  
  
  CONCLUSIONS
  Our data are consistent with a small number of founder carriers of the amyloidogenic TTR V122I (p.Val142Ile) allele in southern West Africa, with no apparent advantage or disadvantage of an allele carrying newborn reaching adulthood. In U.S. African Americans, the allele represents a significant risk for congestive heart failure late in life. If clinical penetrance is similar in African countries with high allele frequencies, then cardiac amyloidosis could also represent a significant cause of heart disease in the elderly in those populations.
authors.affiliation: Veterans Administration Boston Healthcare System and Department of Medicine Boston University School of Medicine Boston Massachusetts.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Jacobson
authors.affiliation: Research Service Veterans Administration Boston Healthcare System Boston Massachusetts.
authors.forename: Alice A
authors.initials: AA
authors.lastname: Alexander
authors.affiliation: Department of Medicine Albert Einstein College of Medicine Bronx New York.
authors.forename: Clement
authors.initials: C
authors.lastname: Tagoe
authors.affiliation: Department of Nutrition Sciences University of Alabama School of Medicine Birmingham Alabama.
authors.forename: W T
authors.initials: WT
authors.lastname: Garvey
authors.affiliation: Department of Genetics Geisel School of Medicine Dartmouth University Hanover New Hampshire.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.affiliation: Departments of Genetics and Biology University of Pennsylvania Philadelphia Pennsylvania.
authors.forename: Sara
authors.initials: S
authors.lastname: Tishkoff
authors.affiliation: Dipartimento di Sanità Pubblica e Malattie Infettive Sapienza Università di Roma Rome Italy.
authors.forename: David
authors.initials: D
authors.lastname: Modiano
authors.affiliation: Centre National de Recherche et Formation sur le Paludisme, Ministère de la Santé Ouagadougou Burkina Faso.
authors.forename: Sodiomon B
authors.initials: SB
authors.lastname: Sirima
authors.affiliation: Hematology Laboratory Hôpital Saint-Louis Paris France.
authors.forename: Issa
authors.initials: I
authors.lastname: Kalidi
authors.affiliation: Institut National de Recherche en Santé Publique Bamako Mali.
authors.forename: Amadou
authors.initials: A
authors.lastname: Toure
authors.affiliation: Department of Molecular and Experimental Medicine The Scripps Research Institute La Jolla California.
authors.forename: Joel N
authors.initials: JN
authors.lastname: Buxbaum
keywords: Africa; amyloidosis; slave trade; transthyretin