African-American TOMM40'523-APOE haplotypes are admixture of West African and Caucasian alleles
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Background: Several studies have demonstrated a lower apolipoprotein E4 (APOE e4) 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 e4 or APOE e3 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 e4 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.
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