Differential Genetic Basis for Pre-Menopausal and Post-Menopausal Salt-Sensitive Hypertension 英文参考文献.docVIP

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Differential Genetic Basis for Pre-Menopausal and Post-Menopausal Salt-Sensitive Hypertension 英文参考文献.doc

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Differential Genetic Basis for Pre-Menopausal and Post-Menopausal Salt-Sensitive Hypertension 英文参考文献

DifferentialGeneticBasisforPre-MenopausalandPost- MenopausalSalt-SensitiveHypertension VictoriaL.M.Herrera,KhristineA.Pasion,AnnMarieMoran,NelsonRuiz-Opazo* SectionofCardiovascularMedicine,DepartmentofMedicine,BostonUniversitySchoolofMedicine,Boston,Massachusetts,UnitedStatesofAmerica 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- hypertensivetherapiesdonotcorrectthispost-menopausalincreasedrisksuggestingadistinctpathogenicframework.We investigatedthehypothesisthatdistinctgeneticdeterminantsmightunderliesusceptibilitytosaltsensitivehypertensionin pre-menopausal andpost-menopausalstates.To determinewhetherdistinctgeneticloci contribute topost-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 S6R)-intercross female rats characterized for blood pressure by radiotelemetry.Givenidenticalenvironmentsandhighsaltchallenge,post-menopausalBPlevelsweresignificantlyhigher 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 significantBP-QTLs(BP-pm1onchromosome13,LOD3.78;BP-pm2onchromosome11,LOD2.76;BP-pm3onchromosome 2,LOD2.61;BP-pm4onchromosome4,LOD2.50)andtwosuggestiveBP-QTLs(BP-pm5onchromosome15,LOD2.37;BP-f1 on chromosome 5, LOD 1.65), four of which (BP-pm2, BP-pm3, BP-pm4, BP-pm5) were unique to this post-menopausal cohort. These data demonstrate distinct polygenic susceptibility underlying post-menopausal salt-sensitive hypertension providing a pathway towards the identification of mechanism-based therapy for post-menopausal hypertension and ensuingtarget-organcomplications. Citation: Herrera V