Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study

R. Li, B. Nicklas, M. Pahor, A. Newman, K. Sutton-Tyrrell, T. Harris, Edward Lakatta, D. C. Bauer, J. Ding, S. Satterfield, S. B. Kritchevsky

Research output: Contribution to journalArticle

Abstract

The role of renin-angiotensin system (RAS) genes on the risk of lower extremity arterial disease (LEAD) in elderly people remains unclear. We assessed the relationship of genetic polymorphisms in RAS: G-6A, T174M and M235T of the angiotensinogen (AGT) gene, and the angiotensin-converting enzyme insertion/deletion (ACE_I/D) variant to the risk of LEAD in the Health, Aging and Body Composition (Health ABC) Study. This analysis included 1228 black and 1306 white men and women whose age ranged between 70 and 79 years at the study enrollment. LEAD was defined as ankle-arm index (AAI) <0.9. Genotype-phenotype associations were estimated by regression analyses with and without adjustment for established cardiovascular disease (CVD) risk factors. The proportion of LEAD was significantly higher in black (21.1%) than that in white elderly people (10.1%, P < 0.0001). The distribution of AGT polymorphisms was also significantly different between black and white participants. There was no statistically significant association between the selected RAS genetic variants and LEAD after adjustment for age, antihypertensive medications, lipid-lowering medication, pack-year smoking, body mass index, low-density lipoprotein cholesterol, and prevalent diabetes and coronary heart disease. However, A-T haplotype of G-6A and M235T interacting with homozygous ACE_II (β = -1.07, P = 0.006) and with ACE inhibitors (β = -1.03, P = 0.01) significantly decreased the risk of LEAD in white but not in black participants after adjustment for the selected CVD risk factors. In conclusion, the study observed a gene-gene and gene-drug interaction for LEAD in the white elderly.

Original languageEnglish (US)
Pages (from-to)673-682
Number of pages10
JournalJournal of Human Hypertension
Volume21
Issue number8
DOIs
StatePublished - Aug 2007
Externally publishedYes

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Angiotensinogen
Peptidyl-Dipeptidase A
Body Composition
Lower Extremity
Health
Renin-Angiotensin System
Genes
Cardiovascular Diseases
Genetic Association Studies
Genetic Polymorphisms
Drug Interactions
Angiotensin-Converting Enzyme Inhibitors
Ankle
LDL Cholesterol
Haplotypes
Antihypertensive Agents
Coronary Disease
Body Mass Index
Arm
Smoking

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study. / Li, R.; Nicklas, B.; Pahor, M.; Newman, A.; Sutton-Tyrrell, K.; Harris, T.; Lakatta, Edward; Bauer, D. C.; Ding, J.; Satterfield, S.; Kritchevsky, S. B.

In: Journal of Human Hypertension, Vol. 21, No. 8, 08.2007, p. 673-682.

Research output: Contribution to journalArticle

Li, R, Nicklas, B, Pahor, M, Newman, A, Sutton-Tyrrell, K, Harris, T, Lakatta, E, Bauer, DC, Ding, J, Satterfield, S & Kritchevsky, SB 2007, 'Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study', Journal of Human Hypertension, vol. 21, no. 8, pp. 673-682. https://doi.org/10.1038/sj.jhh.1002198
Li, R. ; Nicklas, B. ; Pahor, M. ; Newman, A. ; Sutton-Tyrrell, K. ; Harris, T. ; Lakatta, Edward ; Bauer, D. C. ; Ding, J. ; Satterfield, S. ; Kritchevsky, S. B. / Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study. In: Journal of Human Hypertension. 2007 ; Vol. 21, No. 8. pp. 673-682.
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abstract = "The role of renin-angiotensin system (RAS) genes on the risk of lower extremity arterial disease (LEAD) in elderly people remains unclear. We assessed the relationship of genetic polymorphisms in RAS: G-6A, T174M and M235T of the angiotensinogen (AGT) gene, and the angiotensin-converting enzyme insertion/deletion (ACE_I/D) variant to the risk of LEAD in the Health, Aging and Body Composition (Health ABC) Study. This analysis included 1228 black and 1306 white men and women whose age ranged between 70 and 79 years at the study enrollment. LEAD was defined as ankle-arm index (AAI) <0.9. Genotype-phenotype associations were estimated by regression analyses with and without adjustment for established cardiovascular disease (CVD) risk factors. The proportion of LEAD was significantly higher in black (21.1{\%}) than that in white elderly people (10.1{\%}, P < 0.0001). The distribution of AGT polymorphisms was also significantly different between black and white participants. There was no statistically significant association between the selected RAS genetic variants and LEAD after adjustment for age, antihypertensive medications, lipid-lowering medication, pack-year smoking, body mass index, low-density lipoprotein cholesterol, and prevalent diabetes and coronary heart disease. However, A-T haplotype of G-6A and M235T interacting with homozygous ACE_II (β = -1.07, P = 0.006) and with ACE inhibitors (β = -1.03, P = 0.01) significantly decreased the risk of LEAD in white but not in black participants after adjustment for the selected CVD risk factors. In conclusion, the study observed a gene-gene and gene-drug interaction for LEAD in the white elderly.",
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AU - Nicklas, B.

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AU - Newman, A.

AU - Sutton-Tyrrell, K.

AU - Harris, T.

AU - Lakatta, Edward

AU - Bauer, D. C.

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AU - Kritchevsky, S. B.

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