Association between hypertension and variation in the α3- and β-adducin genes in a white population

Ji Guang Wang, Jan A. Staessen, Cristina Barlassina, Robert Fagard, Tatiana Kuznetsova, Harry A. Struijker-Boudier, Laura Zagato, Lorena Citterio, Elisabetta Messaggio, Giuseppe Bianchi

Research output: Contribution to journalArticle

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Abstract

Background. The substitution of tryptophan for glycine at amino acid 460 (Gly460Trp polymorphism) of the α-subunit of the heterodimeric cytoskeleton protein adducin increases renal sodium reabsorption and may be involved in the pathophysiology of essential hypertension. In the present study, we investigated in multivariate analyses whether the risk of hypertension was associated with the C1797T polymorphism of the β-adducin gene. Methods. A total of 1848 subjects randomly selected from a white population were genotyped. Study nurses measured blood pressure at the participants' homes. Results. The frequencies of the α-adducin Trp and β-adducin T alleles were 0.23 and 0.11, respectively. In men (N = 904), the β-adducin T allele was not associated with hypertension [adjusted relative risk (RR) vs. CC homozygotes 0.94, P = 0.77], but T allele carriers had lower plasma renin activity (PRA) and 24-hour urinary aldosterone excretion (P <0.04). In all women (N = 944), β-adducin T allele carriers had a higher risk of hypertension than CC homozygotes (RR 1.81, CI 1.18-2.77, P = 0.007), but similar PRA and 24-hour urinary aldosterone excretion (P > 0.29). In 345 post-menopausal women and 190 users of oral contraceptives, the RRs of hypertension were 2.47 (CI 1.34-4.64, P = 0.003) and 2.56 (CI 0.83-7.86, P = 0.10), respectively. For systolic pressure in women, there was a significant interaction (P = 0.02) between the α- and β-adducin polymorphisms. Only in female carriers of the mutated α-adducin Trp allele was the systolic pressure significantly higher in β-adducin T allele carriers compared with CC homozygotes (+3.8 mm Hg, P = 0.02). Furthermore, in the presence of the mutated α-adducin Trp allele, the RRs associated with the β-adducin T allele were 2.35 (P = 0.01) in all women, 2.92 (P = 0.03) in post-menopausal subjects, and 3.79 (P = 0.09) in users of oral contraceptives. Conclusions. The 1797T allele of the β-adducin gene is associated with increased risk of hypertension in post-menopausal women and in users of oral contraceptives, particularly in the presence of the mutated α-adducin Trp allele. We hypothesize that inhibition of the renin-aldosterone system in men and absence of such a compensatory mechanism in women may explain, at least to some extent, the sexual dimorphism of the blood pressure phenotype in relation to the C1797T β-adducin polymorphism.

Original languageEnglish
Pages (from-to)2152-2159
Number of pages8
JournalKidney International
Volume62
Issue number6
DOIs
Publication statusPublished - 2002

Fingerprint

Hypertension
Alleles
Population
Genes
Oral Contraceptives
Blood Pressure
Homozygote
Aldosterone
Renin
adducin
Cytoskeleton
Tryptophan
Sex Characteristics
Glycine
Multivariate Analysis
Sodium
Nurses
Phenotype
Amino Acids

Keywords

  • Adducin
  • Blood pressure
  • C1797T polymorphism
  • Candidate gene
  • Hypertension
  • Point mutation
  • Renin

ASJC Scopus subject areas

  • Nephrology

Cite this

Wang, J. G., Staessen, J. A., Barlassina, C., Fagard, R., Kuznetsova, T., Struijker-Boudier, H. A., ... Bianchi, G. (2002). Association between hypertension and variation in the α3- and β-adducin genes in a white population. Kidney International, 62(6), 2152-2159. https://doi.org/10.1046/j.1523-1755.2002.00691.x

Association between hypertension and variation in the α3- and β-adducin genes in a white population. / Wang, Ji Guang; Staessen, Jan A.; Barlassina, Cristina; Fagard, Robert; Kuznetsova, Tatiana; Struijker-Boudier, Harry A.; Zagato, Laura; Citterio, Lorena; Messaggio, Elisabetta; Bianchi, Giuseppe.

In: Kidney International, Vol. 62, No. 6, 2002, p. 2152-2159.

Research output: Contribution to journalArticle

Wang, JG, Staessen, JA, Barlassina, C, Fagard, R, Kuznetsova, T, Struijker-Boudier, HA, Zagato, L, Citterio, L, Messaggio, E & Bianchi, G 2002, 'Association between hypertension and variation in the α3- and β-adducin genes in a white population', Kidney International, vol. 62, no. 6, pp. 2152-2159. https://doi.org/10.1046/j.1523-1755.2002.00691.x
Wang JG, Staessen JA, Barlassina C, Fagard R, Kuznetsova T, Struijker-Boudier HA et al. Association between hypertension and variation in the α3- and β-adducin genes in a white population. Kidney International. 2002;62(6):2152-2159. https://doi.org/10.1046/j.1523-1755.2002.00691.x
Wang, Ji Guang ; Staessen, Jan A. ; Barlassina, Cristina ; Fagard, Robert ; Kuznetsova, Tatiana ; Struijker-Boudier, Harry A. ; Zagato, Laura ; Citterio, Lorena ; Messaggio, Elisabetta ; Bianchi, Giuseppe. / Association between hypertension and variation in the α3- and β-adducin genes in a white population. In: Kidney International. 2002 ; Vol. 62, No. 6. pp. 2152-2159.
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abstract = "Background. The substitution of tryptophan for glycine at amino acid 460 (Gly460Trp polymorphism) of the α-subunit of the heterodimeric cytoskeleton protein adducin increases renal sodium reabsorption and may be involved in the pathophysiology of essential hypertension. In the present study, we investigated in multivariate analyses whether the risk of hypertension was associated with the C1797T polymorphism of the β-adducin gene. Methods. A total of 1848 subjects randomly selected from a white population were genotyped. Study nurses measured blood pressure at the participants' homes. Results. The frequencies of the α-adducin Trp and β-adducin T alleles were 0.23 and 0.11, respectively. In men (N = 904), the β-adducin T allele was not associated with hypertension [adjusted relative risk (RR) vs. CC homozygotes 0.94, P = 0.77], but T allele carriers had lower plasma renin activity (PRA) and 24-hour urinary aldosterone excretion (P <0.04). In all women (N = 944), β-adducin T allele carriers had a higher risk of hypertension than CC homozygotes (RR 1.81, CI 1.18-2.77, P = 0.007), but similar PRA and 24-hour urinary aldosterone excretion (P > 0.29). In 345 post-menopausal women and 190 users of oral contraceptives, the RRs of hypertension were 2.47 (CI 1.34-4.64, P = 0.003) and 2.56 (CI 0.83-7.86, P = 0.10), respectively. For systolic pressure in women, there was a significant interaction (P = 0.02) between the α- and β-adducin polymorphisms. Only in female carriers of the mutated α-adducin Trp allele was the systolic pressure significantly higher in β-adducin T allele carriers compared with CC homozygotes (+3.8 mm Hg, P = 0.02). Furthermore, in the presence of the mutated α-adducin Trp allele, the RRs associated with the β-adducin T allele were 2.35 (P = 0.01) in all women, 2.92 (P = 0.03) in post-menopausal subjects, and 3.79 (P = 0.09) in users of oral contraceptives. Conclusions. The 1797T allele of the β-adducin gene is associated with increased risk of hypertension in post-menopausal women and in users of oral contraceptives, particularly in the presence of the mutated α-adducin Trp allele. We hypothesize that inhibition of the renin-aldosterone system in men and absence of such a compensatory mechanism in women may explain, at least to some extent, the sexual dimorphism of the blood pressure phenotype in relation to the C1797T β-adducin polymorphism.",
keywords = "Adducin, Blood pressure, C1797T polymorphism, Candidate gene, Hypertension, Point mutation, Renin",
author = "Wang, {Ji Guang} and Staessen, {Jan A.} and Cristina Barlassina and Robert Fagard and Tatiana Kuznetsova and Struijker-Boudier, {Harry A.} and Laura Zagato and Lorena Citterio and Elisabetta Messaggio and Giuseppe Bianchi",
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TY - JOUR

T1 - Association between hypertension and variation in the α3- and β-adducin genes in a white population

AU - Wang, Ji Guang

AU - Staessen, Jan A.

AU - Barlassina, Cristina

AU - Fagard, Robert

AU - Kuznetsova, Tatiana

AU - Struijker-Boudier, Harry A.

AU - Zagato, Laura

AU - Citterio, Lorena

AU - Messaggio, Elisabetta

AU - Bianchi, Giuseppe

PY - 2002

Y1 - 2002

N2 - Background. The substitution of tryptophan for glycine at amino acid 460 (Gly460Trp polymorphism) of the α-subunit of the heterodimeric cytoskeleton protein adducin increases renal sodium reabsorption and may be involved in the pathophysiology of essential hypertension. In the present study, we investigated in multivariate analyses whether the risk of hypertension was associated with the C1797T polymorphism of the β-adducin gene. Methods. A total of 1848 subjects randomly selected from a white population were genotyped. Study nurses measured blood pressure at the participants' homes. Results. The frequencies of the α-adducin Trp and β-adducin T alleles were 0.23 and 0.11, respectively. In men (N = 904), the β-adducin T allele was not associated with hypertension [adjusted relative risk (RR) vs. CC homozygotes 0.94, P = 0.77], but T allele carriers had lower plasma renin activity (PRA) and 24-hour urinary aldosterone excretion (P <0.04). In all women (N = 944), β-adducin T allele carriers had a higher risk of hypertension than CC homozygotes (RR 1.81, CI 1.18-2.77, P = 0.007), but similar PRA and 24-hour urinary aldosterone excretion (P > 0.29). In 345 post-menopausal women and 190 users of oral contraceptives, the RRs of hypertension were 2.47 (CI 1.34-4.64, P = 0.003) and 2.56 (CI 0.83-7.86, P = 0.10), respectively. For systolic pressure in women, there was a significant interaction (P = 0.02) between the α- and β-adducin polymorphisms. Only in female carriers of the mutated α-adducin Trp allele was the systolic pressure significantly higher in β-adducin T allele carriers compared with CC homozygotes (+3.8 mm Hg, P = 0.02). Furthermore, in the presence of the mutated α-adducin Trp allele, the RRs associated with the β-adducin T allele were 2.35 (P = 0.01) in all women, 2.92 (P = 0.03) in post-menopausal subjects, and 3.79 (P = 0.09) in users of oral contraceptives. Conclusions. The 1797T allele of the β-adducin gene is associated with increased risk of hypertension in post-menopausal women and in users of oral contraceptives, particularly in the presence of the mutated α-adducin Trp allele. We hypothesize that inhibition of the renin-aldosterone system in men and absence of such a compensatory mechanism in women may explain, at least to some extent, the sexual dimorphism of the blood pressure phenotype in relation to the C1797T β-adducin polymorphism.

AB - Background. The substitution of tryptophan for glycine at amino acid 460 (Gly460Trp polymorphism) of the α-subunit of the heterodimeric cytoskeleton protein adducin increases renal sodium reabsorption and may be involved in the pathophysiology of essential hypertension. In the present study, we investigated in multivariate analyses whether the risk of hypertension was associated with the C1797T polymorphism of the β-adducin gene. Methods. A total of 1848 subjects randomly selected from a white population were genotyped. Study nurses measured blood pressure at the participants' homes. Results. The frequencies of the α-adducin Trp and β-adducin T alleles were 0.23 and 0.11, respectively. In men (N = 904), the β-adducin T allele was not associated with hypertension [adjusted relative risk (RR) vs. CC homozygotes 0.94, P = 0.77], but T allele carriers had lower plasma renin activity (PRA) and 24-hour urinary aldosterone excretion (P <0.04). In all women (N = 944), β-adducin T allele carriers had a higher risk of hypertension than CC homozygotes (RR 1.81, CI 1.18-2.77, P = 0.007), but similar PRA and 24-hour urinary aldosterone excretion (P > 0.29). In 345 post-menopausal women and 190 users of oral contraceptives, the RRs of hypertension were 2.47 (CI 1.34-4.64, P = 0.003) and 2.56 (CI 0.83-7.86, P = 0.10), respectively. For systolic pressure in women, there was a significant interaction (P = 0.02) between the α- and β-adducin polymorphisms. Only in female carriers of the mutated α-adducin Trp allele was the systolic pressure significantly higher in β-adducin T allele carriers compared with CC homozygotes (+3.8 mm Hg, P = 0.02). Furthermore, in the presence of the mutated α-adducin Trp allele, the RRs associated with the β-adducin T allele were 2.35 (P = 0.01) in all women, 2.92 (P = 0.03) in post-menopausal subjects, and 3.79 (P = 0.09) in users of oral contraceptives. Conclusions. The 1797T allele of the β-adducin gene is associated with increased risk of hypertension in post-menopausal women and in users of oral contraceptives, particularly in the presence of the mutated α-adducin Trp allele. We hypothesize that inhibition of the renin-aldosterone system in men and absence of such a compensatory mechanism in women may explain, at least to some extent, the sexual dimorphism of the blood pressure phenotype in relation to the C1797T β-adducin polymorphism.

KW - Adducin

KW - Blood pressure

KW - C1797T polymorphism

KW - Candidate gene

KW - Hypertension

KW - Point mutation

KW - Renin

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