Sex-specific effects of AGT-6 and ACE I/D on pulse pressure after 6 months on antihypertensive treatment:: The GenHAT study
Sex-specific effects of AGT-6 and ACE I/D on pulse pressure after 6 months on antihypertensive treatment:: The GenHAT study
复制标题
DOI：
10.1111/j.1469-1809.2007.00381.x
复制
发表时间：
2007-11-01
影响因子：
1.9
通讯作者：
Leiendecker-Foster, C.
中科院分区：
文献类型：
--
作者：
Lynch, A. I.;Arnett, D. K.;Leiendecker-Foster, C.
研究表明脉压 (PP) 是心血管疾病的预测因子，而基因可能会影响 PP 水平。此外，性别可能是 PP 和心血管疾病之间的影响调节因素。本研究探讨了两种肾素-血管紧张素-醛固酮系统 (RAAS) 变异是否以性别特异性方式（基因型与性别相互作用）与 PP 相关。受试者包括 35,048 名年龄超过 55 岁的 GenHAT 研究参与者，其中大约一半是女性，一半是非西班牙裔白人。随机分配四种抗高血压药物之一后 6 个月进行血压测量。考虑的多态性是AGT-6和ACE-I/D。我们采用线性回归来评估相互作用。AGT-6 显示出显着的（p < 0.001）基因型与性别的相互作用。具有“G/G”基因型的男性比携带“A”等位基因的男性具有更高的 PP (0.6 mm HG)，而具有“G/G”基因型的女性比携带“A”等位基因的女性具有更低的 PP (0.7 mm Hg)。四个治疗组中的三个（氯噻酮、氨氯地平和赖诺普利）表明亚组分析中存在一致的相互作用（只有氨氯地平具有统计学显着性，p < 0.001），而多沙唑嗪则不然。这种相互作用在非西班牙裔参与者中很明显，但在西班牙裔参与者中则不然。对于 ACE-I/D，没有检测到基因型与性别相互作用的证据。PP 上基因型与性别相互作用的这一发现有助于我们了解遗传对血压影响的复杂性。
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.