Dementia and Geriatric Cognitive Disorders · 2008 · 29 citations · 33 references
Life SciencesGeneticsMolecular GeneticsDementiaHuman GeneticsMedical GeneticsAlzheimer DiseaseDementia EpidemiologyDementia GeneticsDementia Risk FactorsDown SyndromeNeurodegenerative Disease GeneticsAlzheimer Disease EpidemiologyAlzheimer Disease RiskDementia Risk LociEstrogen Receptor ExpressionEstrogen Receptor GeneticsGenetic Epidemiology Of DementiaRisk Gene VariantsSingle-nucleotide Polymorphisms
BACKGROUND: Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). Two tightly linked polymorphisms (PvuII and XbaI) in the first intron of estrogen receptor 1 (ESR1), the gene for ER-alpha, have been reported to influence estrogen receptor expression and may influence the risk of AD. METHODS: We examined the relation of polymorphisms in ESR1 to the risk of AD in women with Down syndrome. The subjects (181 women with DS, 41-78 years of age) were followed at 14- to 18-month intervals. Information from cognitive assessments, caregiver interviews, medical record reviews and neurological examinations was used to classify dementia. Genomic DNA was genotyped for 5 single-nucleotide polymorphisms in the upstream region and the first exon/intron of the ESR1 gene. Their association with dementia risk was evaluated, adjusting for covariates. RESULTS: Women with at least 1 copy of the C allele at rs2234693 (PvuII) and those homozygous for the C allele at rs2077647 had an almost 3-fold increase in the risk of AD, compared with women without the C allele. The increased risks were independent of the apolipoprotein E genotype. CONCLUSION: These findings support a role for estrogen receptor activity in the development of AD in women with Down syndrome.
33
Haploview: analysis and visualization of LD and haplotype maps
Jeffrey C. Barrett, Ben Fry, Julian Maller et al. · Bioinformatics · 2004 · 14.7K citations · Full text