Sex-Specific Effects of AGT-6 and ACE I/D on Pulse Pressure After 6 Months on Antihypertensive Treatment: The GenHAT Study |
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Authors: | A I Lynch D K Arnett B R Davis E Boerwinkle C E Ford J H Eckfeldt C Leiendecker-Foster |
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Institution: | University of Minnesota, Department of Laboratory Medicine and Pathology, Minneapolis;University of Alabama at Birmingham, Department of Epidemiology, Birmingham;University of Texas-Houston, School of Public Health, Houston |
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Abstract: | Research suggests pulse pressure (PP) is a predictor of cardiovascular disease, and genes likely influence PP levels. Additionally, gender may be an effect modifier between PP and cardiovascular disease. This study addresses whether two renin-angiotensin-aldosterone system ( RAAS ) variants are associated with PP in a sex-specific manner (genotype-by-sex interaction). Subjects comprised 35,048 GenHAT study participants over 55 years old, approximately half were women and half non-Hispanic white. Blood pressure measurements were obtained 6 months after randomization to one of four antihypertensive medications. The polymorphisms considered were AGT-6 and ACE -I/D. We employed linear regression to assess the interaction. AGT-6 showed a significant (p < 0.001) genotype-by-sex interaction. Men with the 'G/G' genotype had a higher PP (0.6 mm HG) than men carrying an 'A' allele, while 'G/G' women had a lower PP (0.7 mm Hg) than women carrying an 'A' allele. Three of the four treatment groups (chlorthalidone, amlodipine and lisinopril) suggested a consistent interaction in sub-group analyses (only amlodipine was statistically significant, p < 0.001), whereas doxazosin did not. The interaction was evident among non-Hispanic participants but not among Hispanic participants. For ACE -I/D no evidence for a genotype-by-sex interaction was detected. This finding of genotype-by-sex interaction on PP helps our understanding of the complexity of genetic effects on blood pressure. |
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Keywords: | pulse pressure blood pressure ACE AGT gene-sex interaction |
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