African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles.

Journal Article (Journal Article)

BACKGROUND: Several studies have demonstrated a lower apolipoprotein E4 (APOE ε4) allele frequency in African-Americans, but yet an increased age-related prevalence of AD. An algorithm for prevention clinical trials incorporating TOMM40'523 (Translocase of Outer Mitochondria Membrane) and APOE depends on accurate TOMM40'523-APOE haplotypes. METHODS: We have compared the APOE and TOMM40'523 phased haplotype frequencies of a 9.5 kb TOMM40/APOE genomic region in West African, Caucasian, and African-American cohorts. RESULTS: African-American haplotype frequency scans of poly-T lengths connected in phase with either APOE ε4 or APOE ε3 differ from both West Africans and Caucasians and represent admixture of several distinct West African and Caucasian haplotypes. A new West African TOMM40'523 haplotype, with APOE ε4 connected to a short TOMM40'523 allele, is observed in African-Americans but not Caucasians. CONCLUSION: These data have therapeutic implications for the age of onset risk algorithm estimates and the design of a prevention trial for African-Americans or other mixed ethnic populations.

Full Text

Duke Authors

Cited Authors

  • Roses, AD; Lutz, MW; Saunders, AM; Goldgaber, D; Saul, R; Sundseth, SS; Akkari, PA; Roses, SM; Gottschalk, WK; Whitfield, KE; Vostrov, AA; Hauser, MA; Allingham, RR; Burns, DK; Chiba-Falek, O; Welsh-Bohmer, KA

Published Date

  • November 2014

Published In

Volume / Issue

  • 10 / 6

Start / End Page

  • 592 - 601.e2

PubMed ID

  • 25260913

Electronic International Standard Serial Number (EISSN)

  • 1552-5279

Digital Object Identifier (DOI)

  • 10.1016/j.jalz.2014.06.009


  • eng

Conference Location

  • United States