Document Detail


The association of genetic variants in interleukin-1 genes with cognition: findings from the cardiovascular health study.
MedLine Citation:
PMID:  21968104     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer's, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta=0.47, 95%CI=0.09, 0.85, p=0.016; rs4251961: beta=-0.36, 95%CI=-0.13,-0.60, p=0.0027; rs931471: beta=0.39, 95%CI=0.13, 0.65, p=0.0032), and the IL1B gene for African Americans (rs1143627: beta=1.6, 95%CI=0.48, 2.8; p=0.006 and rs1143634: beta=2.09, 95%CI=0.39, 3.8; p=0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process.
Authors:
K S Benke; M C Carlson; B Q Doan; J D Walston; Q L Xue; A P Reiner; L P Fried; D E Arking; A Chakravarti; M D Fallin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-24
Journal Detail:
Title:  Experimental gerontology     Volume:  46     ISSN:  1873-6815     ISO Abbreviation:  Exp. Gerontol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-14     Completed Date:  2012-01-17     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0047061     Medline TA:  Exp Gerontol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1010-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Johns Hopkins Medical Institutions, Baltimore, MD, USA. Kelly.Benke@oicr.on.ca
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MeSH Terms
Descriptor/Qualifier:
African Americans / genetics
Aged
Aged, 80 and over
Cognition*
Cognition Disorders / genetics
Dementia / epidemiology,  genetics*,  metabolism
Educational Status
European Continental Ancestry Group / genetics
Female
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Interleukin 1 Receptor Antagonist Protein / genetics*,  metabolism
Interleukin-1alpha / genetics*,  metabolism
Interleukin-1beta / genetics*,  metabolism
Linkage Disequilibrium
Longitudinal Studies
Male
Polymorphism, Single Nucleotide*
Prospective Studies
Risk Factors
United States / epidemiology
Grant Support
ID/Acronym/Agency:
AG15928/AG/NIA NIH HHS; N01 HC-55222/HC/NHLBI NIH HHS; N01-HC-15103/HC/NHLBI NIH HHS; N01-HC-35129/HC/NHLBI NIH HHS; N01-HC-45133/HC/NHLBI NIH HHS; N01-HC-75150/HC/NHLBI NIH HHS; N01-HC-85079/HC/NHLBI NIH HHS; N01-HC-85086/HC/NHLBI NIH HHS; N01HC85081/HL/NHLBI NIH HHS; P30-AG021334/AG/NIA NIH HHS; U01 HL080295/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/IL1RN protein, human; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1alpha; 0/Interleukin-1beta
Comments/Corrections

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