title: The association study between DHCR24 polymorphisms and Alzheimer's disease.
abstract: DHCR24 gene in chromosome 1 encodes seladin 1, a cholesterol synthesizing enzyme. Seladin 1 protects neurons from Abeta(42) mediated toxicity and participates in regulation of Abeta(42) formation by organizing the placement of APP cleaving beta-secretase in cholesterol-rich detergent-resistant membrane domains (DRMs). In Alzheimer's disease (AD) the level of seladin 1 in affected neurons is reduced, DRMs are disorganized and Abeta(42) formation is increased. To examine genetic association of the DHCR24 with AD, we genotyped four single nucleotide polymorphism (SNP) sites (rs638944, rs600491, rs718265, and rs7374) in 414 Finnish AD cases and 459 controls and calculated the allelic and genotypic distribution of both cases and controls. The single locus association analysis indicated that men carrying the T allele of rs600491 had an increased risk of AD (OR 1.7 95% CI 1.2-2.4; P = 0.004, Bonferroni corrected P = 0.048 with 12 tests). We estimated haplotypes of SNPs rs638944 and rs600491 between cases and controls and found overall distribution of haplotypes highly significant (P < 0.001). There was a common protective haplotype TC with frequency of 0.22 in cases and 0.30 in controls (P < 0.001) and a risk haplotype GC with frequency of 0.10 in cases and 0.05 in controls (P < 0.001). We also measured CSF Abeta(42), tau and phosphorylated tau (ptau) levels in a subgroup of AD cases (n = 44) and controls (n = 10) and found that AD cases that carry rs718265 GG had lower levels of Abeta(42) than other genotype carriers. Our findings indicate that DHCR24 gene may be associated with AD risk.
authors.affiliation: Unit of Neurology, Clinical Department, Brain Research Unit, Clinical Research Center, Mediteknia, University of Kuopio, 70211 Kuopio, Finland. riikka.lamsa@uku.fi
authors.forename: R
authors.initials: R
authors.lastname: Lämsä
authors.forename: S
authors.initials: S
authors.lastname: Helisalmi
authors.forename: M
authors.initials: M
authors.lastname: Hiltunen
authors.forename: S-K
authors.initials: SK
authors.lastname: Herukka
authors.forename: T
authors.initials: T
authors.lastname: Tapiola
authors.forename: T
authors.initials: T
authors.lastname: Pirttilä
authors.forename: S
authors.initials: S
authors.lastname: Vepsäläinen
authors.forename: H
authors.initials: H
authors.lastname: Soininen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016875:tau Proteins / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human