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

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

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.

Keywords: Africa; amyloidosis; slave trade; transthyretin.

Figures

Figure 1
Figure 1
Distribution of the TTR V122I allele in Africa (see Table 1). The allele frequencies are indicated by color. Populations from the countries colored light gray were not analyzed.

References

    1. Abecasis, G. R. , Altshuler D., Auton A., Brooks L. D., Durbin R. M., Gibbs R. A., et al. 2010. A map of human genome variation from population‐scale sequencing. Nature 467:1061–1073.
    1. Afolabi, I. , Hamidi A. K., Nakamura M., Jacobs P., Hendrie H., and Benson M. D.. 2000. Transthyretin isoleucine‐122 mutation in African and American blacks. Amyloid 7:121–125.
    1. Alexander, A. , Subramanian N., Buxbaum J. N., and Jacobson D. R.. 2004. Drop‐in, drop‐out allele‐specific PCR: a highly sensitive, single‐tube method. Mol. Biotechnol. 28:171–174.
    1. Ammirati, E. , Marziliano N., Vittori C., Pedrotti P., Bramerio M. A., Motta V., et al. 2012. The first Caucasian patient with p.Val122Ile mutated‐transthyretin cardiac amyloidosis treated with isolated heart transplantation. Amyloid 19:113–117.
    1. Andersson, R. 1976. Familial amyloidosis with polyneuropathy. A clinical study based on patients living in Northern Sweden. Acta Med. Scand. 590:1–64.
    1. Andrade, C. 1952. A peculiar form of peripheral neuropathy. Familial atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain 75:408–427.
    1. Araki, S. , Mawatari S., Ohta M., Nakajima A., and Kuroiwa Y.. 1968. Polyneuritic amyloidosis in a Japanese family. Arch. Neurol. 18:593–602.
    1. Asl, K. H. , Nakamura M., Yamashita T., and Benson M. D.. 2001. Cardiac amyloidosis associated with the transthyretin Ile122 mutation in a Caucasian family. Amyloid 8:263–269.
    1. Bhatia, G. , Tandon A., Patterson N., Aldrich M. C., Ambrosone C. B., Amos C., et al. 2014. Genome‐wide scan of 29,141 African Americans finds no evidence of directional selection since admixture. Am. J. Hum. Genet. 95:437–444.
    1. Bonaiti, B. , Olsson M., Hellman U., Suhr O., Bonaiti‐Pellie C., and Plante‐Bordeneuve V.. 2010. TTR familial amyloid polyneuropathy: does a mitochondrial polymorphism entirely explain the parent‐of‐origin difference in penetrance? Eur. J. Hum. Genet. 16:149–150.
    1. Bryc, K. , Auton A., Nelson M. R., Oksenberg J. R., Hauser S. L., Williams S., et al. 2010. Genome‐wide patterns of population structure and admixture in West Africans and African Americans. Proc. Natl Acad. Sci. USA 107:786–791.
    1. Bryc, K. , Durand E. Y., Macpherson J. M., Reich D., and Mountain J. L.. 2014. The Genetic Ancestry of African Americans, Latinos, and European Americans across the United States. Am. J. Hum. Genet. 96:37–53.
    1. Buxbaum, J. N. 2007. Transthyretin and the Transthyretin Amyloidoses Pp. 259–283 in Uversky V. N. and Fink A., eds. Protein misfolding, aggregation, and conformational diseases. Springer, Santa Cruz, CA.
    1. Buxbaum, J. N. , Roberts A. J., Adame A., and Masliah E.. 2014. Silencing of murine transthyretin and retinol binding protein genes has distinct and shared behavioral and neuropathologic effects. Neuroscience 275:352–364.
    1. Cappelli, F. , Frusconi S., Bergesio F., Grifoni E., Fabbri A., Giuliani C., et al. 2015. The Val142Ile transthyretin cardiac amyloidosis: not only an Afro‐American pathogenic variant? A single‐centre Italian experience J. Cardiovasc. Med. (Hagerstown) 17:122–125.
    1. Cooke, G. S. , Campbell S. J., Fielding K., Sillah J., Manneh K., Sirugo G., et al. 2004. Interleukin‐8 polymorphism is not associated with pulmonary tuberculosis in the gambia. J. Infect. Dis. 189:1545–1546.
    1. Cooper, D. N. , and Youssoufian H.. 1988. The CpG dinucleotide and human genetic disease. Hum. Genet. 78:151–155.
    1. Curtin, P. D. 1969. The Atlantic slave trade: a census. The University of Wisconsin Press, Madison, Milwaukee and London.
    1. Damy, T. , Costes B., Hagege A. A., Donal E., Eicher J. C., Slama M., et al. 2015. Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness. Eur. Heart J. 37:1826–1834.
    1. Gillmore, J. D. , Booth D. R., Pepys M. B., and Hawkins P. N.. 1999. Hereditary cardiac amyloidosis associated with the transthyretin Ile122 mutation in a white man. Heart 82:e2.
    1. Gorevic, P. D. , Prelli F. C., Wright J., Pras M., and Frangione B.. 1989. Systemic Senile Amyloidosis. Identification of a new prealbumin (transthyretin) variant in cardiac tissue: immunologic and biochemical similarity to one form of familial amyloidotic polyneuropathy. J. Clin. Invest. 83:836–843.
    1. Halder, I. , Yang B. Z., Kranzler H. R., Stein M. B., Shriver M. D., and Gelernter J.. 2009. Measurement of admixture proportions and description of admixture structure in different U.S. populations. Hum. Mutat. 30:1299–1309.
    1. Halder, I. , Kip K. E., Mulukutla S. R., Aiyer A. N., Marroquin O. C., Huggins G. S., et al. 2012. Biogeographic ancestry, self‐identified race, and admixture‐phenotype associations in the Heart SCORE Study. Am. J. Epidemiol. 176:146–155.
    1. Hellman, U. , Alarcon F., Lundgren H. E., Suhr O. B., Bonaiti‐Pellie C., and Plante‐Bordeneuve V.. 2008. Heterogeneity of penetrance in familial amyloid polyneuropathy, ATTR Val30Met, in the Swedish population. Amyloid 15:181–186.
    1. Henn, B. M. , Gignoux C., Lin A. A., Oefner P. J., Shen P., Scozzari R., et al. 2008. Y‐chromosomal evidence of a pastoralist migration through Tanzania to southern Africa. Proc. Natl Acad. Sci. USA 105:10693–10698.
    1. Hornstrup, L. S. , Frikke‐Schmidt R., Nordestgaard B. G., and Tybjaerg‐Hansen A.. 2013. Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy. Arterioscler. Thromb. Vasc. Biol. 33:1441–1447.
    1. Iorio, A. , De A. F., Di G. M., Luigetti M., Pradotto L., Mauro A., et al. 2014. Most recent common ancestor of TTR Val30Met mutation in Italian population and its potential role in genotype‐phenotype correlation. Amyloid 22:73–78.
    1. Jackson, B. A. , Wilson J. L., Kirbah S., Sidney S. S., Rosenberger J., Bassie L., et al. 2005. Mitochondrial DNA genetic diversityamong four ethnic groups in Sierra Leone. Am. J. Phys. Anthropol. 128:156–163.
    1. Jacobson, D. R. 1992. A specific test for transthyretin 122 (Val‐Ile) based on PCR‐primer introduced restriction analysis (PCR‐PIRA): confirmation of the gene frequency in Blacks. Am. J. Hum. Genet. 50:195–198.
    1. Jacobson, D. R. , Gorevic P. D., and Buxbaum J. N.. 1990. A homozygous transthyretin variant associated with senile systemic amyloidosis: evidence for a late‐onset disease of genetic etiology. Am. J. Hum. Genet. 47:127–136.
    1. Jacobson, D. R. , Alves I. L., Saraiva M. J., Thibodeau S. N., and Buxbaum J. N.. 1995. Transthyretin Ser 6 gene frequency in individuals without amyloidosis. Hum. Genet. 95:308–312.
    1. Jacobson, D. R. , Schneider J., Sobel M., Yang J., Malendowicz S., Sobol J., et al. 1998. The origin of the transthyretin Ile 122 allele: haplotype analysis and population studies Pp. 227–229 in Kyle R. A., ed. Amyloid and amyloidosis. Parthenon; NY, London.
    1. Jacobson, D. R. , Alexander A. A., Tagoe C., and Buxbaum J. N.. 2015. Prevalence of the amyloidogenic transthyretin (TTR) V122I allele in 14 333 African‐Americans. Amyloid 22:171–174.
    1. Johnson, S. M. , Connelly S., Fearns C., Powers E. T., and Kelly J. W.. 2012. The transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory‐agency‐approved drug. J. Mol. Biol. 42:185–203.
    1. Kalidi, I. , Fofana Y., Rahly A. A., Bochu V., Dehay C., Gony J., et al. 1988. Study of HLA antigens in a population of Mali (West Africa). Tissue Antigens 31:98–102.
    1. Koike, H. , Misu K., Ikeda S., Ando Y., Nakazato M., Ando E., et al. 2002. Type I (transthyretin Met30) familial amyloid polyneuropathy in Japan: early‐ versus late‐onset form. Arch. Neurol. 59:1771–1776.
    1. Kostrikis, L. G. , Tyagi S., Mhlanga M. M., Ho D. D., and Kramer F. R.. 1998. Spectralgenotyping of human alleles. Science 279:1228–1229.
    1. Li, X. , Masliah E., Reixach N., and Buxbaum J. N.. 2011. Neuronal production of transthyretin in human and murine Alzheimer's disease: is it protective? J. Neurosci. 31:12483–12490.
    1. Mersha, T. B. , and Abebe T.. 2015. Self‐reported race/ethnicity in the age of genomic research: its potential impact on understanding health disparities. Hum. Genomics 9:1.
    1. Modiano, D. , Petrarca V., Sirima B. S., Luoni G., Nebie I., Diallo D. A., et al. 1999. Different response to Plasmodium falciparum in west African sympatric ethnic groups: possible implications for malaria control strategies. Parassitologia 41:193–197.
    1. Murray, T. , Beaty T. H., Mathias R. A., Rafaels N., Grant A. V., Faruque M. U., et al. 2010. African and non‐African admixture components in African Americans and an African Caribbean population. Genet. Epidemiol. 34:561–568.
    1. Nichols, W. C. , Liepnieks J. J., Snyder E. L., and Benson M. D.. 1991. Senile cardiac amyloidosis associated with homozygosity for a transthyretin variant (ILE‐122). J. Lab. Clin. Med. 117:175–180.
    1. Norgren, N. , Hellman U., Ericzon B. G., Olsson M., and Suhr O. B.. 2012. Allele specific expression of the transthyretin gene in swedish patients with hereditary transthyretin amyloidosis (ATTR V30M) is similar between the two alleles. PLoS ONE 7:e49981.
    1. Olsson, M. , Hellman U., Plante‐Bordeneuve V., Jonasson J., Lang K., and Suhr O. B.. 2008. Mitochondrial haplogroup is associated with the phenotype of familial amyloidosis with polyneuropathy in Swedish and French patients. Clin. Genet. 11:1–7.
    1. Olsson, M. , Norgren N., Obayashi K., Plante‐Bordeneuve V., Suhr O. B., Cederquist K., et al. 2010. A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers. BMC Med. Genet. 11:130.
    1. Polimanti, R. , Di G. M., Manfellotto D., and Fuciarelli M.. 2013. Functional variation of the transthyretin gene among human populations and its correlation with amyloidosis phenotypes. Amyloid 20:256–262.
    1. Polimanti, R. , Di G. M., Manfellotto D., and Fuciarelli M.. 2014. In silico analysis of TTR gene (coding and non‐coding regions, and interactive network) and its implications in transthyretin‐related amyloidosis. Amyloid 21:154–162.
    1. Reddi, H. V. , Jenkins S., Theis J., Thomas B. C., Connors L. H., van Rhee F., et al. 2014. Homozygosity for the V122I mutation in transthyretin is associated with earlier onset of cardiac amyloidosis in the African American population in the seventh decade of life. J. Mol. Diagn. 16:68–74.
    1. Reilly, M. M. , Adams D., Davis M., Said G., and Harding A. E.. 1995. Haplotype analysis of French, British and other European patients with familial amyloid polyneuropathy (MET30 and TYR77). J. Neurol. 242:664–668.
    1. Reixach, N. , Deechongkit S., Jiang X., Kelly J. W., and Buxbaum J. N.. 2004. Tissue damage in the amyloidoses: transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc. Natl Acad. Sci. USA 101:2817–2822.
    1. Rousseau, J. , Mathew C. G., Rees J. S., du Toit E., Botha M. C., and Harley E. H.. 1985. Incidence of Hb Barts and alpha‐thalassaemia genotypes in a South African population. Acta Haematol. 73:159–162.
    1. Rowczenio, D. M. , Noor I., Gillmore J. D., Lachmann H. J., Whelan C., Hawkins P. N., et al. 2014. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations. Hum. Mutat. 35:E2403–E2412.
    1. Santos, D. , Coelho T., Alves‐Ferreira M., Sequeiros J., Mendonca D., Alonso I., et al. 2015. Variants in RBP4 and AR genes modulate age at onset in familial amyloid polyneuropathy (FAP ATTRV30M). Euro. J. Hum. Gen. 24:756–760.
    1. Sirugo, G. , Sam O., Nyan O., Pinder M., Hill A. V., Kwiatkowski D., et al. 2004. A national DNA bank in The Gambia, West Africa, and genomic research in developing countries. Nat. Genet. 36:785–786.
    1. Soares, M. L. , Coelho T., Sousa A., Holmgren G., Saraiva M. J., Kastner D. L., et al. 2004. Haplotypes and DNA sequence variation within and surrounding the transthyretin gene: genotype‐phenotype correlations in familial amyloid polyneuropathy (V30M) in Portugal and Sweden. Eur. J. Hum. Genet. 12:225–237.
    1. Soares, M. L. , Coelho T., Sousa A., Batalov S., Conceicao I., Sales‐Luis M. L., et al. 2005. Susceptibility and modifier genes in Portuguese transthyretin V30M amyloid polyneuropathy: complexity in a single‐gene disease. Hum. Mol. Genet. 14:543–553.
    1. Sousa, A. , Coelho T., and Sequeiros J.. 1991. Parental transmission and age‐of‐onset in familial amyloidotic polineuropathy (Portuguese type). Amyloid and Amyloidosis 1990. p. 691–693.
    1. Sousa, J. C. , Grandela C., Fernandez‐Ruiz J., de Miguel R., de Sousa L., Magalhaes A. I., et al. 2004. Transthyretin is involved in depression‐like behaviour and exploratory activity. J. Neurochem. 88:1052–1058.
    1. Tandon, A. , Patterson N., and Reich D.. 2011. Ancestry informative marker panels for African Americans based on subsets of commercially available SNP arrays. Genet. Epidemiol. 35:80–83.
    1. Tishkoff, S. A. , Reed F. A., Friedlaender F. R., Ehret C., Ranciaro A., Froment A., et al. 2009. The genetic structure and history of Africans and African Americans. Science 324:1035–1044.
    1. Vulliamy, T. J. , Othman A., Town M., Nathwani A., Falusi A. G., Mason P. J., et al. 1991. Polymorphic sites in the African population detected by sequence analysis of the glucose‐6‐phosphate dehydrogenase gene outline the evolution of the variants A and A‐. Proc. Natl Acad. Sci. USA 88:8568–8571.
    1. Wallace, M. R. , Naylor S. L., Kluve‐Beckerman B., Long G. L., McDonald L., Shows T. B., et al. 1985. Localization of the human prealbumin gene to chromosome 18. Biochem. Biophys. Res. Commun. 129:753–758.
    1. Wang, X. , Cattaneo F., Ryno L., Hulleman J., Reixach N., and Buxbaum J. N.. 2014. The systemic amyloid precursor transthyretin (TTR) behaves as a neuronal stress protein regulated by HSF1 in SH‐SY5Y human neuroblastoma cells and APP23 Alzheimer's disease model mice. J. Neurosci. 34:7253–7265.
    1. Williams, S. M. , Addy J. H., Phillips J. A. III, Dai M., Kpodonu J., Afful J., et al. 2000. Combinations of variations in multiple genes are associated with hypertension. Hypertension 36:2–6.
    1. Yoshioka, K. , Furuya H., Sasaki H., Saraiva M. J. M., Costa P. P., and Sakaki Y.. 1989. Haplotype analysis of familial amyloidotic polyneuropathy. Evidence for multiple origins of the Val‐Met mutation most common to the disease. Hum. Genet. 82:9–13.
    1. Zaros, C. , Genin E., Hellman U., Saporta M., Languille L., and Wadington‐Cruz M.. 2008. On the origin of the transthyretin Val30Met familial amyloid polyneuropathy. Ann. Hum. Genet. 72:478–484.
    1. Zimmerman, P. A. , Phadke P. M., Lee A., Elson L. H., Aruajo E., Guderian R., et al. 1995. Migration of a novel DQA1* allele (DQA1*0502) from African origin to North and South America. Hum. Immunol. 42:233–240.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa