Apolipoprotein E, ɛ4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region
Marie‐Christine Chartier‐Harlin, Matthew Parfitt, Sylvie Legrain, Jordi Pérez‐Tur, Thierry Brousseau, Alun Evans, Claudine Berr, Odile Vldal et al.. Human Molecular Genetics, 1994-01-01
Topic: Genetics and APOE
An association between the 19q13.2 chromosomal region and Alzheimer's disease (AD) has been reported in AD families and for sporadic AD. Recent observations provide evidence that the ɛ4 allele of the apolipoprotein E gene (APOE), located in this region, is a risk factor for late-onset AD. Within this region, other genes possibly involved in the pathophyslology of AD and in strong linkage disequilibrium with the APOE locus may be responsible for this association. To test this hypothesis, we analysed the allelic distribution of four polymorphic genetic markers flanking the APOE gene (D19S178 (CA)n repeat, D19S47 (CA)n repeat, APOCI Hpal restriction fragment length polymorphism, APOCII (CA)n repeat). We performed these analyses in a sample of late-onset sporadic cases (n = 36) versus controls (n = 38), and in a sample of early-onset sporadic cases (n = 34) versus controls (n = 36). Early-onset cases were analysed for two cut-offs with late-onset: less than 60 and less than 65. We observed a significant increased frequency of the APOE ɛ4 allele in late-onset and early-onset AD with ages at onset less than 60 and less than 65. The adjusted odds ratio (OR) of the bearers of at least one APOE ɛ4 allele was 4.10 ([1.84; 9.16]) when estimated in both populations with a logistic regression model. Surprisingly, the odds ratio of the bearers of at least one APOE ɛ2 allele was also significant and equal to 0.11 ([0.02; 0.50]) suggesting a possible protective effect. An association with the disease was also observed for the long alleles of APOCII (CA)n repeat in the late-onset AD (OR = 3.56, [1.19; 10.70]), and for the short alleles of D19S178 (CA)n repeat In the early-onset AD (OR = 4.44, [1.27; 15.49]). In conclusion, APOE is a major risk factor for early- and late-onset sporadic AD. The combination of the APOE polymorphism with flanking markers located within the APOE locus significantly Improved the association with the disease in both populations.
Key findings
- We performed these analyses in a sample of late-onset sporadic cases (n = 36) versus controls (n = 38), and in a sample of early-onset sporadic cases (n = 34) versus controls (n = 36).
- We observed a significant increased frequency of the APOE ɛ4 allele in late-onset and early-onset AD with ages at onset less than 60 and less than 65.
- Surprisingly, the odds ratio of the bearers of at least one APOE ɛ2 allele was also significant and equal to 0.11 ([0.02; 0.50]) suggesting a possible protective effect.
- In conclusion, APOE is a major risk factor for early- and late-onset sporadic AD.
- The combination of the APOE polymorphism with flanking markers located within the APOE locus significantly Improved the association with the disease in both populations.
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Study details
- Participants36
- Effect sizeOR = 3.56; OR = 4.44
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Human Molecular Genetics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 1994 — older than 20 years, still counted |
| Sample size | 1 / 4 | 36 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8069300) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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APA 7th
Chartier‐Harlin, M., Parfitt, M., Legrain, S., Pérez‐Tur, J., Brousseau, T., Evans, A., et al. (1994). Apolipoprotein E, ɛ4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. Human Molecular Genetics. https://doi.org/10.1093/hmg/3.4.569
Vancouver
Chartier‐Harlin M, Parfitt M, Legrain S, Pérez‐Tur J, Brousseau T, Evans A, et al. Apolipoprotein E, ɛ4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. Human Molecular Genetics. 1994. doi:10.1093/hmg/3.4.569. PMID: 8069300.
BibTeX
@article{chartierharlin1994-8069300,
author = {Chartier‐Harlin, Marie‐Christine and Parfitt, Matthew and Legrain, Sylvie and Pérez‐Tur, Jordi and Brousseau, Thierry and Evans, Alun and Berr, Claudine and Vldal, Odile and others},
title = {{Apolipoprotein E, ɛ4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region}},
journal = {Human Molecular Genetics},
year = {1994},
doi = {10.1093/hmg/3.4.569},
pmid = {8069300},
url = {https://doi.org/10.1093/hmg/3.4.569}
}
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