Evidence map›Paper›PMID 40374698›Full record

ArticleScientific reports2025

Search for the elusive haplotype of the APOE polymorphism associated with Alzheimer's disease.

Asma Naseer Cheema, Kang-Hsien Fan, Elizabeth Lawrence, Narges Zafari, Ruyu Shi, Muhammad Muaaz Aslam, Vibha Acharya, Alayna Jean Holderman, Annie Bedison, Eleanor Feingold and 1 more

Abstract read
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In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Asma Naseer CheemaDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Kang-Hsien FanDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Elizabeth LawrenceDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Narges ZafariDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Ruyu ShiDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Muhammad Muaaz AslamDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Vibha AcharyaDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Alayna Jean HoldermanDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Annie BedisonDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Eleanor FeingoldDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
M Ilyas KambohDepartment of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA. kamboh@pitt.edu.

Funding

Research Education ComponentP30AG066468 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI C. Elizabeth Shaaban · 2020 to 2026
$29.4M
National Institutes of Health, United States R01 AG064877 and P30 AG066468NIA NIH HHS P30 AG066468
6 · The paper itself

Abstract

The common APOE2/E3/E4 polymorphism is determined by two-site haplotypes: C112R and R158C. Due to strong linkage disequilibrium (LD) between the two sites, three of the four expected haplotypes/alleles (E2, E3, E4) have been observed. Compared to the most common E3 haplotype (C112-R158), E4 (R112-R158) results from a mutation at codon 112, while E2 (C112-C158) results from a mutation at codon 158. The fourth haplotype (E5) having mutations at both sites (R112-C158) has been reported only as an incidental finding in three kindreds. To our knowledge, no systematic search has been done to determine its distribution in the general population. The objective of this study was to search for the elusive haplotype by subcloning a DNA fragment of 177 bp from 355 subjects with the APOE 2/4 genotype followed by sequencing as well as in 11,647 subjects genotyped by TaqMan assays. No example of the E5 haplotype was observed, suggesting it might have a minimum effect, if any, on Alzheimer's disease risk. Under the assumption of strong LD between the two sites, the estimated probability for the occurrence of the E5 haplotype by recombination event is 3.31E-08, which is similar to 5.58E-08 probability obtained by recurrent point mutation.

Indexed as

Alzheimer DiseaseApolipoproteins EGenetic Predisposition to DiseaseHaplotypesPolymorphism, GeneticAgedAllelesFemaleGenotypeHumansLinkage DisequilibriumMalePolymorphism, Single NucleotideApoE protein, humanApolipoproteins EAPOE haplotypeCloningGenotypingRecombination, point mutationSequencing

Identifiers

PMID40374698
PMCPMC12081911

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