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 journalArticlepeer-review

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

Keywords

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

ASJC Scopus subject areas

  • Nephrology

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