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Apolipoprotein E polymorphisms in frontotemporal lobar degeneration: a meta-analysis.

Elisa Rubino¹, Alessandro Vacca, Flora Govone

¹Neurology II, Department of Neuroscience, University of Torino, Torino, Italy.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association

|May 22, 2013

Summary

The apolipoprotein E (APOE) ε4 allele is linked to increased risk of frontotemporal lobar degeneration (FTLD). This systematic review confirms APOE gene polymorphism as a significant risk factor for FTLD.

Keywords:

APOE Case–control study Frontotemporal lobar degeneration Meta-analysis Polymorphism

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Area of Science:

Neurogenetics
Neurodegenerative Diseases
Human Genetics

Background:

Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of neurodegenerative disorders.
Previous studies on apolipoprotein E (APOE) polymorphisms and FTLD risk have yielded inconsistent results.
The role of APOE gene variations in FTLD pathogenesis requires further clarification.

Purpose of the Study:

To systematically review and quantify the association between APOE gene polymorphisms and FTLD risk.
To determine if APOE allele carriage is a significant risk factor for developing FTLD.
To consolidate existing evidence regarding APOE and FTLD.

Main Methods:

A systematic review and meta-analysis of 28 case-control studies investigating APOE and FTLD.
Inclusion criteria focused on studies with clinical or pathological FTLD diagnosis and APOE allelic/genotypic data.
Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random effects models.

Main Results:

Carriage of the APOE ε2 allele showed no significant effect on FTLD risk.
The APOE ε4 allele was significantly associated with an increased risk of FTLD (OR=1.94).
A gene-dosage effect for the APOE ε4 allele was observed, indicating higher risk with more ε4 alleles.

Conclusions:

This meta-analysis provides robust evidence for a significant association between the APOE ε4 allele and frontotemporal lobar degeneration.
APOE ε4 is confirmed as a risk factor for FTLD.
Further research may explore the mechanisms underlying this association.