The association study between DHCR24 polymorphisms and Alzheimer's disease.
R Lämsä1, S Helisalmi, M Hiltunen
1Unit of Neurology, Clinical Department, Brain Research Unit, Clinical Research Center, Mediteknia, University of Kuopio, 70211 Kuopio, Finland. riikka.lamsa@uku.fi
Summary
The DHCR24 gene, encoding seladin 1, shows association with Alzheimer's disease (AD) risk. Specific genetic variations in DHCR24 may influence AD susceptibility and amyloid-beta 42 (Abeta(42)) levels.
Area of Science:
- Neurogenetics
- Molecular Biology
- Biochemistry
Background:
- DHCR24 gene encodes seladin 1, a cholesterol-synthesizing enzyme crucial for neuronal protection against Abeta(42) toxicity.
- Seladin 1 regulates Abeta(42) formation by influencing beta-secretase placement in membrane domains.
- Reduced seladin 1 levels and disorganized membrane domains are observed in Alzheimer's disease (AD) brains, correlating with increased Abeta(42).
Purpose of the Study:
- To investigate the genetic association between the DHCR24 gene and Alzheimer's disease (AD) risk.
- To analyze the relationship between specific DHCR24 single nucleotide polymorphisms (SNPs) and AD susceptibility.
- To explore the correlation between DHCR24 genotypes and cerebrospinal fluid (CSF) biomarker levels in AD.
Main Methods:
- Genotyping of four DHCR24 SNPs (rs638944, rs600491, rs718265, rs7374) in 414 Finnish AD cases and 459 controls.
- Allelic and genotypic distribution analysis for association studies.
- Haplotype estimation for SNPs rs638944 and rs600491.
- Measurement of CSF Abeta(42), tau, and phosphorylated tau (ptau) levels in a subgroup of participants.
Main Results:
- Men carrying the T allele of rs600491 showed an increased risk of AD (OR 1.7, P = 0.004).
- Significant associations were found for haplotypes of rs638944 and rs600491, with a protective TC haplotype and a risk GC haplotype identified.
- AD cases with the rs718265 GG genotype exhibited lower CSF Abeta(42) levels compared to other genotype carriers.
Conclusions:
- The DHCR24 gene is potentially associated with Alzheimer's disease risk.
- Specific genetic variations within DHCR24 may influence AD susceptibility, particularly in men.
- DHCR24 genotypes may correlate with AD pathological biomarkers like Abeta(42) levels.
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