P2‐135: the Tomm40 Repeat Does Not Provide Protection for Ad for Apoe4 Carriers With Local Genomic African Ancestry (lga)
Year: 2019
Type: article
Study design: Observational Study
Abstract: We have shown the difference in risk between African and Non-Hispanic White (NHW) carriers of ApoE4 is due to a factor in LGA surrounding the ApoE4 allele. The Translocase of Outer Mitochondrial Membrane 40 gene (TOMM40) lies within that LGA and contains a polymorphic intronic poly-T variant known as TOMM40-523’. Previous studies have suggested differences in repeat length may contribute to risk differences between these ethnic groups. However, these studies used global ancestry in the analysis and not LGA. We investigated the role of the TOMM40-523’ repeat variant as a potential LGA AD risk modifier. We designed PCR primers spanning the TOMM40-523’ locus and genotyped DNA (blood) from both cases and controls of 100 African-American (AA) individuals and 100 NHW individuals, i.e. 50 ApoE3/3 AA individuals and 50 ApoE4/4 AA with African LGA; 50 ApoE3/3 NHW individuals and 50 ApoE4/4 NHW individuals with NHW LGA. Repeat length was determined by fragment analysis. Data were analyzed by two methods, both taking into account APOE genotype, LGA and AD affection status: 1) samples were binned into variant length alleles, and 2) samples were analyzed as a linear function of number of T's. Both analytical models were consistent in that they did not identify a protective role for TOMM40-523’ amongst LGA African ApoE4/4 carriers. We did identify an inverse relationship between TOMM40-523’ repeat length and presence of AD (p=0.008; OR=0.15; CI=0.04-0.59), in the NHW ApoE 3/3 carriers such as previously reported by Cruchaga et al. (2011). These data do not support that the TOMM40-523’ repeat is the protective effect for AD seen in African ApoE4/4 individuals. Our findings are novel in that they adjust for local ancestry.
Source: Alzheimer s & Dementia
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2981224373