BACKGROUND: The genetic dissection of a polygenic, multifactorial, quantitative disease such as arterial hypertension is hampered by a large environmental variance and by genetic heterogeneity. METHODS: To reduce the environmental variance, we measured the pressor response to a saline load (PRSL) and the basal plasma renin activity (PRA) under very controlled conditions in 145 essential hypertensive patients, as they may have the most direct clinical expression of the putative genetic alteration in renal Na handling and blood pressure (BP) regulation caused by the alpha-adducin and angiotensin-converting enzyme (ACE) polymorphism. RESULTS: PRSL was smaller in patients homozygous for the wild-type (Gly460) variant of alpha-adducin compared with that of patients bearing at least one copy of the 460Trp variant (2.5 +/- 0.6 vs. 7.0 +/- 0.9 mm Hg, P = 0.0001), whereas the ACE genotype was not associated with differences in PRSL. Both alpha-adducin and ACE affect PRA, with lower values correlated with the number of 460Trp or D alleles (P = 0.019 and 0.017, respectively). Most important, alpha-adducin and ACE interact epistatically in determining the PRSL, doubling the variance explained when epistasis is taken into account (variance from 7.7 to 15.5%). CONCLUSION: These findings support the involvement of ACE and alpha-adducin in PRSL and PRA control, which are of paramount importance in setting the BP level and its response to therapy.
BACKGROUND: The genetic dissection of a polygenic, multifactorial, quantitative disease such as arterial hypertension is hampered by a large environmental variance and by genetic heterogeneity. METHODS: To reduce the environmental variance, we measured the pressor response to a saline load (PRSL) and the basal plasma renin activity (PRA) under very controlled conditions in 145 essential hypertensive patients, as they may have the most direct clinical expression of the putative genetic alteration in renal Na handling and blood pressure (BP) regulation caused by the alpha-adducin and angiotensin-converting enzyme (ACE) polymorphism. RESULTS: PRSL was smaller in patients homozygous for the wild-type (Gly460) variant of alpha-adducin compared with that of patients bearing at least one copy of the 460Trp variant (2.5 +/- 0.6 vs. 7.0 +/- 0.9 mm Hg, P = 0.0001), whereas the ACE genotype was not associated with differences in PRSL. Both alpha-adducin and ACE affect PRA, with lower values correlated with the number of 460Trp or D alleles (P = 0.019 and 0.017, respectively). Most important, alpha-adducin and ACE interact epistatically in determining the PRSL, doubling the variance explained when epistasis is taken into account (variance from 7.7 to 15.5%). CONCLUSION: These findings support the involvement of ACE and alpha-adducin in PRSL and PRA control, which are of paramount importance in setting the BP level and its response to therapy.
Authors: May E Montasser; Lawrence C Shimmin; Donfeng Gu; Jing Chen; Charles Gu; Tanika N Kelly; Cashell E Jaquish; Treva Rice; D C Rao; Jie Cao; Jichun Chen; De-Pei Liu; Paul Whelton; Jiang He; James E Hixson Journal: J Hypertens Date: 2010-04 Impact factor: 4.844
Authors: Tanika N Kelly; Treva K Rice; Dongfeng Gu; James E Hixson; Jing Chen; Depei Liu; Cashell E Jaquish; Lydia A Bazzano; Dongsheng Hu; Jixiang Ma; C Charles Gu; Jianfeng Huang; L Lee Hamm; Jiang He Journal: Am J Hypertens Date: 2009-07-02 Impact factor: 2.689
Authors: Ji-Guang Wang; Lifang Liu; Laura Zagato; Jinxiang Xie; Robert Fagard; Kugen Jin; Jinxiang Wang; Yan Li; Giuseppe Bianchi; Jan A Staessen; Lisheng Liu Journal: J Mol Med (Berl) Date: 2004-09-18 Impact factor: 4.599
Authors: Tobias Gerhard; Yan Gong; Amber L Beitelshees; Xianyun Mao; Maximilian T Lobmeyer; Rhonda M Cooper-DeHoff; Taimour Y Langaee; Nicholas J Schork; Mark D Shriver; Carl J Pepine; Julie A Johnson Journal: Am Heart J Date: 2008-06-20 Impact factor: 4.749