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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 volume 21, pages 673–682 (2007)Cite this article

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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Acknowledgements

We acknowledge all Health ABC participants. We appreciate Elizabeth Webb for her editing of this manuscript. This study was supported by grants NIH NIA NO1-AG-6-2101, NO1-AG-6-2103, and NO1-AG-6-2106; R01 AG18702-01A1 and P30 AG021332-01.

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Authors and Affiliations

  1. Department of Preventive Medicine, Center for Genomics and Bioinformatics, University of Tennessee Health Science Center, Memphis, TN, USA

    R Li

  2. Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    B Nicklas, J Ding & S B Kritchevsky

  3. Department of Aging and Geriatric Research, University of Florida College of Medicine, Gainesville, FL, USA

    M Pahor

  4. Division of Geriatric Medicine, University of Pittsburgh, PA, USA

    A Newman

  5. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    K Sutton-Tyrrell

  6. Geriatric Epidemiology, National Institute on Aging, National Institutes of Health, USA

    T Harris

  7. Laboratory of Cardiovascular Science and Cardiovascular Function Section, National Institute on Aging, National Institutes of Health, USA

    E Lakatta

  8. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    D C Bauer

  9. Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

    S Satterfield

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  1. R Li
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Correspondence to R Li.

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Li, R., Nicklas, B., Pahor, M. et al. Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study. J Hum Hypertens 21, 673–682 (2007). https://doi.org/10.1038/sj.jhh.1002198

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