African‐American TOMM40'523‐APOEhaplotypes are admixture of West African and Caucasian alleles

• DOI: 10.1016/j.jalz.2014.06.009
• Publication Date: 2014-09-26T02:45:45Z
• Authors: Allen D. Roses; Michael W. Lutz; Ann M. Saunders; Dmitry Goldgaber; Robert Saul; Scott S. Sundseth; P. Anthony Akkari; Stephanie M. Roses; W. Kirby Gottschalk; Keith E. Whitfield; Alexander A. Vostrov; Michael A. Hauser; R. Rand Allingham; Daniel K. Burns; Ornit Chiba‐Falek; Kathleen A. Welsh...
• Keywords: Male; 0301 basic medicine; haplotypes; Phased Sanger sequencing; Poly T; Epidemiology; Clinical Neurology; 610; Black People; TOMM40; Caucasian; Yoruban; White People; Cohort Studies; Cellular and Molecular Neuroscience; 03 medical and health sciences; age of onset; Apolipoproteins E; 0302 clinical medicine; Developmental Neuroscience; Gene Frequency; 616; Mitochondrial Precursor Protein Import Complex Proteins; Complex disease genetics; Humans; African-American; Phylogenetic analysis; Health Policy; Membrane Transport Proteins; Alzheimer's disease; United States; Black or African American; Psychiatry and Mental health; Africa, Western; Population admixture; Haplotypes; Female; Geriatrics and Gerontology; APOE

AbstractBackgroundSeveral studies have demonstrated a lower apolipoprotein E4 (APOEε4) 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) andAPOEdepends on accurate TOMM40'523‐APOEhaplotypes.MethodsWe have compared theAPOEand TOMM40'523 phased haplotype frequencies of a 9.5 kb TOMM40/APOEgenomic region in West African, Caucasian, and African‐American cohorts.ResultsAfrican‐American haplotype frequency scans of poly‐T lengths connected in phase with eitherAPOEε4 orAPOEε3 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, withAPOEε4 connected to a short TOMM40'523 allele, is observed in African‐Americans but not Caucasians.ConclusionThese 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.