Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2005-2-15
pubmed:abstractText
Alzheimer disease (AD) is a polygenic multifactorial disorder. Several studies suggested that the neuroprotective effect of estrogen was based on an APOE-dependent mechanism. The goals of the current study were to determine if the genes involved in estrogen metabolism were linked to the risk of AD and find out if there was an interaction between estrogen-metabolizing gene polymorphisms and the APOE epsilon4 allele in the risk of prevalent AD. We investigated 66 patients with AD and 86 age- and gender-matched normal subjects. The polymorphisms of APOE and estrogen-metabolizing genes CYP17, CYP1A1 and COMT were examined. No association was found between each estrogen-metabolizing gene polymorphism and AD. However, the COMT HH genotype and APOE epsilon4 allele had a synergistic effect on the risk of AD. Taking subjects with epsilon4-epsilon4-/HH- as reference, the risk of developing AD in subjects with one epsilon4 allele (epsilon4+epsilon4-/HH-) was 2.6 (95% confidence interval, CI, 0.7- 9.1); however, the risk in subjects with both HH and one epsilon4 (epsilon4+epsilon4-/HH+) increased to 3.6 (95% CI 1.2-10.6). The subjects with homozygous epsilon4 still had the highest risk in developing AD (odds ratio 6.6, 95% CI 0.6-69.6). The p value of the linear trend test for this regression model was 0.004. It is possible that a high metabolism of estrogen by COMT may have reduced the protective effect of estrogen in AD. Further studies to clarify this interaction may improve our understanding of the generic risks for AD.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1420-8008
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
120-5
pubmed:dateRevised
2008-3-24
pubmed:meshHeading
pubmed-meshheading:15591802-Aged, pubmed-meshheading:15591802-Aged, 80 and over, pubmed-meshheading:15591802-Alleles, pubmed-meshheading:15591802-Alzheimer Disease, pubmed-meshheading:15591802-Apolipoprotein E4, pubmed-meshheading:15591802-Apolipoproteins E, pubmed-meshheading:15591802-Catechol O-Methyltransferase, pubmed-meshheading:15591802-Cytochrome P-450 CYP1A1, pubmed-meshheading:15591802-Estrogens, pubmed-meshheading:15591802-Female, pubmed-meshheading:15591802-Gene Frequency, pubmed-meshheading:15591802-Genetic Predisposition to Disease, pubmed-meshheading:15591802-Genotype, pubmed-meshheading:15591802-Homozygote, pubmed-meshheading:15591802-Humans, pubmed-meshheading:15591802-Male, pubmed-meshheading:15591802-Multifactorial Inheritance, pubmed-meshheading:15591802-Polymorphism, Genetic, pubmed-meshheading:15591802-Risk, pubmed-meshheading:15591802-Steroid 17-alpha-Hydroxylase, pubmed-meshheading:15591802-Taiwan
pubmed:year
2005
pubmed:articleTitle
Estrogen-metabolizing gene COMT polymorphism synergistic APOE epsilon4 allele increases the risk of Alzheimer disease.
pubmed:affiliation
The Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't