differential genetic basis for pre-menopausal and post-menopausal salt-sensitive hypertension微分绝经前和绝经后的食盐过敏高血压的遗传基础.pdfVIP

Differential Genetic Basis for Pre-Menopausal and Post- Menopausal Salt-Sensitive Hypertension Victoria L. M. Herrera, Khristine A. Pasion, Ann Marie Moran, Nelson Ruiz-Opazo* Section of Cardiovascular Medicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America Abstract Essential hypertension affects 75% of post-menopausal women in the United States causing greater cardiovascular complications compared with age-matched men and pre-menopausal women. Hormone replacement and current anti- hypertensive therapies do not correct this post-menopausal increased risk suggesting a distinct pathogenic framework. We investigated the hypothesis that distinct genetic determinants might underlie susceptibility to salt sensitive hypertension in pre-menopausal and post-menopausal states. To determine whether distinct genetic loci contribute to post-menopausal salt-sensitive hypertension, we performed a genome-wide scan for quantitative trait loci (QTLs) affecting blood pressure (BP) in 16-month old post-menopausal F2 (Dahl S 6R)-intercross female rats characterized for blood pressure by radiotelemetry. Given identical environments and high salt challenge, post-menopausal BP levels were significantly higher than observed in pre-menopausal (post-menopausal versus pre-menopausal SBP, P,0.0001) and ovariectomized (post- menopausal versus ovariectomized SBP, P,0.001) F2-intercross female rats. We detected four significant to highly significant BP-QTLs (BP-pm1 on chromosome 13, LOD 3.78; BP-pm2 on chromosome 11, LOD 2.76; BP-pm3 on chromosome 2, LOD 2.61; BP-pm4 on chromosome 4, LOD 2.50) and two suggestive BP-QTLs (BP-pm5 on chromosome 15, LOD 2.37; BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm