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Updated: Jul 3, 2026

Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
The RELN locus in Alzheimer's disease
Davide Seripa1, Maria Giovanna Matera, Marilisa Franceschi
1Geriatric Unit & Gerontology-Geriatric Research Laboratory, Department of Medical Sciences, I.R.C.C.S. Casa Sollievo dalla Sofferenza, San Giovanni Rotondo (FG), I-71013, Italy. dseripa@operapadrepio.it
Genetic variations in the RELN gene may influence Alzheimer's disease (AD) development, particularly in females. Specific RELN gene polymorphisms showed differing distributions between AD patients and controls, especially in women.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Alzheimer's disease (AD) pathogenesis involves the apolipoprotein E (apoE) pathway, including the serine protease Reelin (RELN).
- Reported sex-related differences in AD epidemiology and pathology warrant investigation into sex-specific genetic contributions.
Purpose of the Study:
- To investigate the potential role of RELN gene variants in the pathogenesis of sporadic Alzheimer's disease.
- To explore sex-specific associations between RELN polymorphisms and AD risk.
Main Methods:
- Genotyping of three RELN polymorphisms (5'UTR repeat, rs607755, rs2229874) in 223 Caucasian sporadic AD patients and 181 controls.
- Analysis of genotype distributions between cases and controls, stratified by sex.
- Adjustment for apolipoprotein E (APOE) genotypes.
Main Results:
- Significant differences in 5'UTR and rs607755 genotype distributions were observed between AD patients and controls.
- No significant differences were found for the rs2229874 genotype.
- Sex-stratified analysis revealed significant genotype differences in females but not in males, even after adjusting for APOE status.
Conclusions:
- RELN gene variants may contribute to Alzheimer's disease pathogenesis.
- The association between RELN variants and AD appears to be more pronounced in females.
- Further research is needed to elucidate the specific mechanisms underlying the role of RELN in AD, particularly in women.
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