The AGT-6 polymorphism demonstrated a significant genotype-by-sex interaction on pulse pressure at 6 months (P<0.001), with 'G/G' men having 0.6 mm Hg higher and 'G/G' women having 0.7 mm Hg lower pulse pressure.
RCT (n=35,048)
Do the AGT-6 and ACE-I/D genetic variants have a sex-specific effect on pulse pressure in older adults on antihypertensive treatment?
The AGT-6 polymorphism demonstrates a significant sex-specific effect on pulse pressure in older adults receiving antihypertensive therapy, highlighting the complexity of genetic influences on blood pressure.
p-value: p=<0.001
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.
Lynch et al. (Sat,) conducted a rct in Hypertension (n=35,048). AGT-6 and ACE-I/D polymorphisms vs. Alternative alleles was evaluated on Genotype-by-sex interaction on pulse pressure (p=<0.001). The AGT-6 polymorphism demonstrated a significant genotype-by-sex interaction on pulse pressure at 6 months (P<0.001), with 'G/G' men having 0.6 mm Hg higher and 'G/G' women having 0.7 mm Hg lower pulse pressure.