APOE ε4-TOMM40 '523 haplotypes and the risk of Alzheimer's disease in older Caucasian and African Americans.

PLoS One
Authors
Keywords
Abstract

Patterns of linkage between the ε4 allele of Apolipoprotein E (APOE) and '523 poly-T alleles in the adjacent gene, TOMM40, differ between Caucasian and African Americans. The extent to which this difference affects the risk of Alzheimer's disease (AD) is unclear. We compared the APOE ε4-TOMM40 '523 haplotypes between older Caucasian and African Americans, and examined their relationship with AD dementia. Data came from three community based cohort studies of diverse participants. APOE genotypes were determined by polymorphisms of rs429358 and rs7412. TOMM40 '523 genotypes were defined by the poly-T repeat length of rs10524523 (short ['523-S]: poly-T ≤ 19, long ['523-L]: 20 ≤ poly-T ≤ 29, and very long ['523-VL]: poly-T ≥ 30). Cox proportional hazards models examined the effect of haplotype variation on the risk of incident AD dementia. A total of 1,848 Caucasian and 540 African American individuals were included in the study. In Caucasians, nearly none (0.8%) of the non-ε4 carriers and almost all (94.2%) of the ε4 carriers had '523-L. The classification was highly concordant. Each ε4 allele doubled the risk for AD dementia and the dose effect was evident. Almost identical effect size and effect pattern were observed for TOMM40 '523-L. In African Americans, nearly none (1.1%) of the non-ε4 carriers had '523-L, but only 47.8% of the ε4 carriers had '523-L. The concordance was weaker compared with Caucasians. The effect patterns on incident AD dementia differed distinctively between ε4 and '523-L carriers. Further, both genotypic and allelic data support that among African Americans the ε4-'523-L haplotype had stronger effect on risk of AD dementia than other ε4-'523 haplotypes.

Year of Publication
2017
Journal
PLoS One
Volume
12
Issue
7
Pages
e0180356
Date Published
2017
ISSN
1932-6203
DOI
10.1371/journal.pone.0180356
PubMed ID
28672022
PubMed Central ID
PMC5495438
Links
Grant list
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
RF1 AG022018 / AG / NIA NIH HHS / United States