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Sex-specific effects of ACE I/D and AGT-M235T on pulse pressure: the HyperGEN Study

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Abstract

Evidence shows that an elevated pulse pressure (PP) may lead to an increased risk of cardiovascular morbidity and mortality. There is also evidence that PP is a sexually dimorphic trait, and that genetic factors influence inter-individual variation in PP. The aim of this project was to assess the genotype-by-sex interaction on PP in a sample of mostly hypertensive African American and White participants using candidate genes involved in the renin–angiotensin–aldosterone system. Subjects were participants in the HyperGEN Study, including men (43%) and women (57%) over the age of 55 years (mean age = 65). Candidate gene polymorphisms used were ACE insertion/deletion (1,789 subjects genotyped) and AGT-M235T (1,800 subjects genotyped). We employed linear regression methods to assess the genotype-by-sex interaction. For ACE, genotype-by-sex interaction on PP was detected (P = 0.04): the “D/D” genotype predicted a 2.2 mmHg higher pulse pressure among women, but a 1.2 mmHg lower PP among men, compared to those with an “I” allele, after adjusting for age, weight, height, ethnicity, and antihypertension medication use. A similar interaction was found for systolic blood pressure. The genotype-by-sex interaction was consistent across ethnicity. The interaction was evident among those on antihypertensive medications (P = 0.05), but not among those not taking such medications (P = 0.55). In our analysis of AGT, no evidence of a genotype-by-sex interaction affecting PP, SBP, or DBP was detected. This evidence for a genotype-by-sex interaction helps our understanding of the complex genetic underpinnings of blood pressure phenotypes.

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Acknowledgments

Supported in part by grants HL55673, HL54471, HL 54472, HL54473, HL54495, HL54496, HL54497, HL54509 HL 54515 and HL007972 from the National Heart, Lung and Blood Institute, Bethesda, MD, and grant M10RR0047-34 (GCRC) from the National Institutes of Health, Bethesda, MD.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    Amy I. Lynch & John H. Eckfeldt

  2. Department of Epidemiology, University of Alabama at Birmingham, RPHB 220E, 1530 3rd Avenue South, Birmingham, AL, 55294-0022, USA

    Donna K. Arnett

  3. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA

    James S. Pankow & Michael B. Miller

  4. Division of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Kari E. North

  5. Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA

    Steven C. Hunt

  6. Division of Biostatistics, Washington University School of Medicine, St Louis, MO, USA

    Dabeeru C. Rao

  7. Division of Aging, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Luc Djoussé

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  1. Amy I. Lynch
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  2. Donna K. Arnett
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Correspondence to Donna K. Arnett.

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Lynch, A.I., Arnett, D.K., Pankow, J.S. et al. Sex-specific effects of ACE I/D and AGT-M235T on pulse pressure: the HyperGEN Study. Hum Genet 122, 33–40 (2007). https://doi.org/10.1007/s00439-007-0370-y

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  • DOI: https://doi.org/10.1007/s00439-007-0370-y

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