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

Publication ,  Journal Article
Yu, L; Lutz, MW; Wilson, RS; Burns, DK; Roses, AD; Saunders, AM; Yang, J; Gaiteri, C; De Jager, PL; Barnes, LL; Bennett, DA
Published in: PLoS One
2017

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2017

Volume

12

Issue

7

Start / End Page

e0180356

Location

United States

Related Subject Headings

  • White People
  • Risk Factors
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • Humans
  • Haplotypes
  • Genetic Predisposition to Disease
  • Genetic Linkage
 

Citation

APA
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Yu, L., Lutz, M. W., Wilson, R. S., Burns, D. K., Roses, A. D., Saunders, A. M., … Bennett, D. A. (2017). APOE ε4-TOMM40 '523 haplotypes and the risk of Alzheimer's disease in older Caucasian and African Americans. PLoS One, 12(7), e0180356. https://doi.org/10.1371/journal.pone.0180356
Yu, Lei, Michael W. Lutz, Robert S. Wilson, Daniel K. Burns, Allen D. Roses, Ann M. Saunders, Jingyun Yang, et al. “APOE ε4-TOMM40 '523 haplotypes and the risk of Alzheimer's disease in older Caucasian and African Americans.PLoS One 12, no. 7 (2017): e0180356. https://doi.org/10.1371/journal.pone.0180356.
Yu L, Lutz MW, Wilson RS, Burns DK, Roses AD, Saunders AM, et al. APOE ε4-TOMM40 '523 haplotypes and the risk of Alzheimer's disease in older Caucasian and African Americans. PLoS One. 2017;12(7):e0180356.
Yu, Lei, et al. “APOE ε4-TOMM40 '523 haplotypes and the risk of Alzheimer's disease in older Caucasian and African Americans.PLoS One, vol. 12, no. 7, 2017, p. e0180356. Pubmed, doi:10.1371/journal.pone.0180356.
Yu L, Lutz MW, Wilson RS, Burns DK, Roses AD, Saunders AM, Yang J, Gaiteri C, De Jager PL, Barnes LL, Bennett DA. APOE ε4-TOMM40 '523 haplotypes and the risk of Alzheimer's disease in older Caucasian and African Americans. PLoS One. 2017;12(7):e0180356.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2017

Volume

12

Issue

7

Start / End Page

e0180356

Location

United States

Related Subject Headings

  • White People
  • Risk Factors
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Middle Aged
  • Membrane Transport Proteins
  • Male
  • Humans
  • Haplotypes
  • Genetic Predisposition to Disease
  • Genetic Linkage