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Sex‐Specific Effects of AGT‐6 and ACE I/D on Pulse Pressure After 6 Months on Antihypertensive Treatment: The GenHAT Study
Author(s) -
Lynch A. I.,
Arnett D. K.,
Davis B. R.,
Boerwinkle E.,
Ford C. E.,
Eckfeldt J. H.,
LeiendeckerFoster C.
Publication year - 2007
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2007.00381.x
Subject(s) - blood pressure , pulse pressure , medicine , pulse (music) , endocrinology , cardiology , physics , detector , optics
Summary 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.