Renin angiotensin system gene polymorphisms modify angiotensin-converting enzyme inhibitors' effect on cognitive function: The health, aging and body composition study

Ihab Hajjar, Stephen Kritchevsky, Anne B. Newman, Rongling Li, Kristine Yaffe, Eleanor Marie Simonsick, Lewis A. Lipsitz

Research output: Contribution to journalArticle

Abstract

Objectives: To investigate the effect of polymorphisms in renin angiotensin system genes on the association between angiotensin-converting enzyme inhibitor (ACEI) exposure and global and executive cognitive function in the Health, Aging and Body Composition study. Design: Cohort study. Setting: Community. Participants: Three thousand seventy-five participants: mean age 73.6, 58% Caucasian, 52% female, 15% taking ACE-Is, 8 years of follow-up. Measurements: The outcomes were longitudinal change in Executive Clock Drawing Test-1 (CLOX1), the Digit Symbol Substitution test, and the Modified Mini-Mental State Examination. The genetic polymorphisms included angiotensin-converting enzyme insertion deletion (ACEID) in the ACE gene and the M235T and 6AG polymorphisms in the angiotensinogen (AGT) gene. Results: For the CLOX1 outcome, there was significant interaction between 6AG and M235T polymorphisms in the AGT gene and angiotensin-converting enzyme inhibitors (ACE-Is) in Caucasian participants (P=.01 for both polymorphisms) independent of blood pressure levels. Specifically, ACE-I exposure was protective against CLOX1 score decline in carriers of the AA genotype of the 6AG and the CC genotype of the M235T (for the ACE-I vs non-ACE-I groups, P=.01 for 6AG and P=.005 for M235T) but not the other genotypes. These associations were not significant with other cognitive tests, with ACEID, or in African Americans. Conclusion: ACE-Is may provide a protective effect on executive function in Caucasians with AGT gene polymorphisms known to be associated with greater renin angiotensin system activity. If confirmed in a pharmacogenetic trial, ACE-Is may be found to have additional cognitive protection in a select group of elderly individuals.

Original languageEnglish (US)
Pages (from-to)1035-1042
Number of pages8
JournalJournal of the American Geriatrics Society
Volume58
Issue number6
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Renin-Angiotensin System
Body Composition
Angiotensin-Converting Enzyme Inhibitors
Cognition
Angiotensinogen
Health
Genes
Executive Function
Genotype
Peptidyl-Dipeptidase A
Pharmacogenetics
Genetic Polymorphisms
African Americans
Cohort Studies
Blood Pressure

Keywords

  • Angiotensin- converting enzyme inhibitors
  • Angiotensinogen gene
  • Cognitive function
  • Hypertension

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

Renin angiotensin system gene polymorphisms modify angiotensin-converting enzyme inhibitors' effect on cognitive function : The health, aging and body composition study. / Hajjar, Ihab; Kritchevsky, Stephen; Newman, Anne B.; Li, Rongling; Yaffe, Kristine; Simonsick, Eleanor Marie; Lipsitz, Lewis A.

In: Journal of the American Geriatrics Society, Vol. 58, No. 6, 2010, p. 1035-1042.

Research output: Contribution to journalArticle

@article{59e1fadbd5c541e8a76bc567c8b69b86,
title = "Renin angiotensin system gene polymorphisms modify angiotensin-converting enzyme inhibitors' effect on cognitive function: The health, aging and body composition study",
abstract = "Objectives: To investigate the effect of polymorphisms in renin angiotensin system genes on the association between angiotensin-converting enzyme inhibitor (ACEI) exposure and global and executive cognitive function in the Health, Aging and Body Composition study. Design: Cohort study. Setting: Community. Participants: Three thousand seventy-five participants: mean age 73.6, 58{\%} Caucasian, 52{\%} female, 15{\%} taking ACE-Is, 8 years of follow-up. Measurements: The outcomes were longitudinal change in Executive Clock Drawing Test-1 (CLOX1), the Digit Symbol Substitution test, and the Modified Mini-Mental State Examination. The genetic polymorphisms included angiotensin-converting enzyme insertion deletion (ACEID) in the ACE gene and the M235T and 6AG polymorphisms in the angiotensinogen (AGT) gene. Results: For the CLOX1 outcome, there was significant interaction between 6AG and M235T polymorphisms in the AGT gene and angiotensin-converting enzyme inhibitors (ACE-Is) in Caucasian participants (P=.01 for both polymorphisms) independent of blood pressure levels. Specifically, ACE-I exposure was protective against CLOX1 score decline in carriers of the AA genotype of the 6AG and the CC genotype of the M235T (for the ACE-I vs non-ACE-I groups, P=.01 for 6AG and P=.005 for M235T) but not the other genotypes. These associations were not significant with other cognitive tests, with ACEID, or in African Americans. Conclusion: ACE-Is may provide a protective effect on executive function in Caucasians with AGT gene polymorphisms known to be associated with greater renin angiotensin system activity. If confirmed in a pharmacogenetic trial, ACE-Is may be found to have additional cognitive protection in a select group of elderly individuals.",
keywords = "Angiotensin- converting enzyme inhibitors, Angiotensinogen gene, Cognitive function, Hypertension",
author = "Ihab Hajjar and Stephen Kritchevsky and Newman, {Anne B.} and Rongling Li and Kristine Yaffe and Simonsick, {Eleanor Marie} and Lipsitz, {Lewis A.}",
year = "2010",
doi = "10.1111/j.1532-5415.2010.02860.x",
language = "English (US)",
volume = "58",
pages = "1035--1042",
journal = "Journal of the American Geriatrics Society",
issn = "0002-8614",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Renin angiotensin system gene polymorphisms modify angiotensin-converting enzyme inhibitors' effect on cognitive function

T2 - The health, aging and body composition study

AU - Hajjar, Ihab

AU - Kritchevsky, Stephen

AU - Newman, Anne B.

AU - Li, Rongling

AU - Yaffe, Kristine

AU - Simonsick, Eleanor Marie

AU - Lipsitz, Lewis A.

PY - 2010

Y1 - 2010

N2 - Objectives: To investigate the effect of polymorphisms in renin angiotensin system genes on the association between angiotensin-converting enzyme inhibitor (ACEI) exposure and global and executive cognitive function in the Health, Aging and Body Composition study. Design: Cohort study. Setting: Community. Participants: Three thousand seventy-five participants: mean age 73.6, 58% Caucasian, 52% female, 15% taking ACE-Is, 8 years of follow-up. Measurements: The outcomes were longitudinal change in Executive Clock Drawing Test-1 (CLOX1), the Digit Symbol Substitution test, and the Modified Mini-Mental State Examination. The genetic polymorphisms included angiotensin-converting enzyme insertion deletion (ACEID) in the ACE gene and the M235T and 6AG polymorphisms in the angiotensinogen (AGT) gene. Results: For the CLOX1 outcome, there was significant interaction between 6AG and M235T polymorphisms in the AGT gene and angiotensin-converting enzyme inhibitors (ACE-Is) in Caucasian participants (P=.01 for both polymorphisms) independent of blood pressure levels. Specifically, ACE-I exposure was protective against CLOX1 score decline in carriers of the AA genotype of the 6AG and the CC genotype of the M235T (for the ACE-I vs non-ACE-I groups, P=.01 for 6AG and P=.005 for M235T) but not the other genotypes. These associations were not significant with other cognitive tests, with ACEID, or in African Americans. Conclusion: ACE-Is may provide a protective effect on executive function in Caucasians with AGT gene polymorphisms known to be associated with greater renin angiotensin system activity. If confirmed in a pharmacogenetic trial, ACE-Is may be found to have additional cognitive protection in a select group of elderly individuals.

AB - Objectives: To investigate the effect of polymorphisms in renin angiotensin system genes on the association between angiotensin-converting enzyme inhibitor (ACEI) exposure and global and executive cognitive function in the Health, Aging and Body Composition study. Design: Cohort study. Setting: Community. Participants: Three thousand seventy-five participants: mean age 73.6, 58% Caucasian, 52% female, 15% taking ACE-Is, 8 years of follow-up. Measurements: The outcomes were longitudinal change in Executive Clock Drawing Test-1 (CLOX1), the Digit Symbol Substitution test, and the Modified Mini-Mental State Examination. The genetic polymorphisms included angiotensin-converting enzyme insertion deletion (ACEID) in the ACE gene and the M235T and 6AG polymorphisms in the angiotensinogen (AGT) gene. Results: For the CLOX1 outcome, there was significant interaction between 6AG and M235T polymorphisms in the AGT gene and angiotensin-converting enzyme inhibitors (ACE-Is) in Caucasian participants (P=.01 for both polymorphisms) independent of blood pressure levels. Specifically, ACE-I exposure was protective against CLOX1 score decline in carriers of the AA genotype of the 6AG and the CC genotype of the M235T (for the ACE-I vs non-ACE-I groups, P=.01 for 6AG and P=.005 for M235T) but not the other genotypes. These associations were not significant with other cognitive tests, with ACEID, or in African Americans. Conclusion: ACE-Is may provide a protective effect on executive function in Caucasians with AGT gene polymorphisms known to be associated with greater renin angiotensin system activity. If confirmed in a pharmacogenetic trial, ACE-Is may be found to have additional cognitive protection in a select group of elderly individuals.

KW - Angiotensin- converting enzyme inhibitors

KW - Angiotensinogen gene

KW - Cognitive function

KW - Hypertension

UR - http://www.scopus.com/inward/record.url?scp=77953118951&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953118951&partnerID=8YFLogxK

U2 - 10.1111/j.1532-5415.2010.02860.x

DO - 10.1111/j.1532-5415.2010.02860.x

M3 - Article

C2 - 20722844

AN - SCOPUS:77953118951

VL - 58

SP - 1035

EP - 1042

JO - Journal of the American Geriatrics Society

JF - Journal of the American Geriatrics Society

SN - 0002-8614

IS - 6

ER -