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

Amy I. Lynch, Donna K. Arnett, James S. Pankow, Michael B. Miller, Kari E. North, John H. Eckfeldt, Steven C. Hunt, Dabeeru C. Rao, Luc Djoussé

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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.

Original languageEnglish
Pages (from-to)33-40
Number of pages8
JournalHuman Genetics
Volume122
Issue number1
DOIs
Publication statusPublished - 1 Aug 2007

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Lynch, A. I., Arnett, D. K., Pankow, J. S., Miller, M. B., North, K. E., Eckfeldt, J. H., Hunt, S. C., Rao, D. C., & Djoussé, L. (2007). Sex-specific effects of ACE I/D and AGT-M235T on pulse pressure: The HyperGEN Study. Human Genetics, 122(1), 33-40. https://doi.org/10.1007/s00439-007-0370-y