Synergistic effect of α-adducin and ACE genes causes blood pressure changes with body sodium and volume expansion. 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 α-adducin and angiotensin-converting enzyme (ACE) polymorphism. Results PRSL was smaller in patients homozygous for the wild-type (Gly460) variant of α-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 α-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, α-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 α-adducin in PRSL and PRA control, which are of paramount importance in setting the BP level and its response to therapy.

Synergistic effect of alpha-adducin and ACE genes causes blood pressure changes with body sodium and volume expansion / C. Barlassina, N.J. Schork, P. Manunta, L. Citterio, M. Sciarrone, G. Lanella, G. Bianchi, D. Cusi. - In: KIDNEY INTERNATIONAL. - ISSN 0085-2538. - 57:3(2000 Mar), pp. 1083-1090.

Synergistic effect of alpha-adducin and ACE genes causes blood pressure changes with body sodium and volume expansion

C. Barlassina
Primo
;
D. Cusi
Ultimo
2000

Abstract

Synergistic effect of α-adducin and ACE genes causes blood pressure changes with body sodium and volume expansion. 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 α-adducin and angiotensin-converting enzyme (ACE) polymorphism. Results PRSL was smaller in patients homozygous for the wild-type (Gly460) variant of α-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 α-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, α-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 α-adducin in PRSL and PRA control, which are of paramount importance in setting the BP level and its response to therapy.
Angiotensin converting enzyme; Epistatic interaction; Genetics; Hypertension; Pressor response; Renin-angiotensin system
Settore MED/14 - Nefrologia
mar-2000
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/211223
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