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. 1997 May 10;349(9062):1353-7.
doi: 10.1016/S0140-6736(97)01029-5.

Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension

D Cusi  1 , C Barlassina, T Azzani, G Casari, L Citterio, M Devoto, N Glorioso, C Lanzani, P Manunta, M Righetti, R Rivera, P Stella, C Troffa, L Zagato, G Bianchi
Affiliations

Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension

D Cusi et al. Lancet. .

Erratum in

  • Lancet 1997 Aug 16;350(9076):524

Abstract

Background: Abnormalities in renal sodium transport may be involved in hypertension. Adducin, an alpha/beta heterodimeric protein found in the renal tubule is thought to regulate ion transport through changes in the actin cytoskeleton. We investigated whether an alpha-adducin polymorphism (Gly 460 Trp) is involved in essential hypertension in two separate populations.

Methods: Linkage analysis of three DNA markers at different distances from the alpha-adducin locus (20-2500 kb) was done in 137 hypertensive sibling-pairs. 477 hypertensive and 322 normotensive individuals were genotyped for the alpha-adducin polymorphism. The blood-pressure response to acute and chronic changes in sodium balance was studied in hypertensive individuals with and without the 460 Trp alpha-adducin allele.

Findings: Significant linkage was found for all three markers in the sibling-pair study. The extra shared alleles (9.1%, 6.5%, and 4.7%) and the significance level for linkage (p = 0.0006, p = 0.0119, and p = 0.0211) both decreased with increasing distance from the alpha-adducin locus. There was a significant association between the 460 Trp mutation and hypertension (p = 0.0003). In the salt-sensitivity test, to assess the acute blood-pressure response to changes in body sodium in 86 hypertensive patients, the decrease in mean arterial pressure was greater in 65 patients who were heterozygous for the mutant allele (Gly/Trp) than in 21 wild-type homozygotes (Gly/Gly) (mean decrease 15.9 [SE 2.0] vs 7.4 [1.3] mm Hg; p = 0.001). Similarly, 21 heterozygous hypertensive patients showed a greater fall in mean arterial pressure in response to 2 months' treatment with hydrochlorothiazide than did 37 wild-type homozygous hypertensive patients (mean decrease 14.7 [2.2] vs 6.8 [1.4] mm Hg; p = 0.002).

Interpretation: Our findings of significant linkage of the alpha-adducin locus to essential hypertension and greater sensitivity to changes in sodium balance among patients with the mutant allele suggest that alpha-adducin is associated with a salt-sensitive form of essential hypertension. We suggest the alpha-adducin polymorphism may identify hypertensive patients who will benefit from diuretic treatment or manoeuvres to reduce total body sodium.

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Comment in

  • Private genes, public health.
    Harrap SB. Harrap SB. Lancet. 1997 May 10;349(9062):1338-9. doi: 10.1016/S0140-6736(05)63198-4. Lancet. 1997. PMID: 9149692 No abstract available.
  • Polymorphism of alpha-adducin and hypertension.
    Iwai N, Tamaki S, Nakamura Y, Kinoshita M. Iwai N, et al. Lancet. 1997 Aug 2;350(9074):369. doi: 10.1016/S0140-6736(05)63430-7. Lancet. 1997. PMID: 9251667 No abstract available.

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