The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa

Daniel R. Jacobson, Alice A. Alexander, Clement E. Tagoe, W. T. Garvey, Scott M. Williams, Sara Tishkoff, David Modiano, Sodiomon B. Sirima, Issa Kalidi, Amadou Toure, Joel N. Buxbaum

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)548-556
Number of pages9
JournalMolecular Genetics and Genomic Medicine
Volume4
Issue number5
DOIs
StatePublished - Sep 1 2016

Fingerprint

Prealbumin
Gene Frequency
Alleles
Amyloidosis
African Americans
Sierra Leone
Guinea
Burkina Faso
Cote d'Ivoire
Southern Africa
Ghana
Western Africa
Penetrance
Nigeria
Codon
Population
Heart Diseases
Heart Failure
Genotype
Newborn Infant

Keywords

  • Africa
  • Amyloidosis
  • Slave trade
  • Transthyretin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Jacobson, D. R., Alexander, A. A., Tagoe, C. E., Garvey, W. T., Williams, S. M., Tishkoff, S., ... Buxbaum, J. N. (2016). The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa. Molecular Genetics and Genomic Medicine, 4(5), 548-556. https://doi.org/10.1002/mgg3.231

The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa. / Jacobson, Daniel R.; Alexander, Alice A.; Tagoe, Clement E.; Garvey, W. T.; Williams, Scott M.; Tishkoff, Sara; Modiano, David; Sirima, Sodiomon B.; Kalidi, Issa; Toure, Amadou; Buxbaum, Joel N.

In: Molecular Genetics and Genomic Medicine, Vol. 4, No. 5, 01.09.2016, p. 548-556.

Research output: Contribution to journalArticle

Jacobson, DR, Alexander, AA, Tagoe, CE, Garvey, WT, Williams, SM, Tishkoff, S, Modiano, D, Sirima, SB, Kalidi, I, Toure, A & Buxbaum, JN 2016, 'The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa', Molecular Genetics and Genomic Medicine, vol. 4, no. 5, pp. 548-556. https://doi.org/10.1002/mgg3.231
Jacobson, Daniel R. ; Alexander, Alice A. ; Tagoe, Clement E. ; Garvey, W. T. ; Williams, Scott M. ; Tishkoff, Sara ; Modiano, David ; Sirima, Sodiomon B. ; Kalidi, Issa ; Toure, Amadou ; Buxbaum, Joel N. / The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa. In: Molecular Genetics and Genomic Medicine. 2016 ; Vol. 4, No. 5. pp. 548-556.
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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.",
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