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Intra-erythrocyte cation concentrations in relation to the C1797T β-adducin polymorphism in a general population

Journal of Human Hypertension volume 21, pages 387–392 (2007)Cite this article

Abstract

Genetic variability in the ADD1 (Gly460Trp) and ADD2 (C1797T) subunits of the cytoskeleton protein adducin plays a role in the pathogenesis of hypertension, possibly via changes in intracellular cation concentrations. ADD2 1797CC homozygous men have decreased erythrocyte count and hematocrit. We investigated possible association between intra-erythrocyte cations and the adducin polymorphisms. In 259 subjects (mean age 47.7 years), we measured intra-erythrocyte Na+ [iNa], K+ [iK] and Mg2+ [iMg], serum cations and adducin genotypes. Genotype frequencies (ADD1: GlyGly 61.5%, Trp 38.5%; ADD2: CC 80.4%, T 19.6%) complied with Hardy–Weinberg proportions. In men, ADD2 CC homozygotes (n=100) compared to T-carriers (n=23) had slightly lower iK (85.8 versus 87.5 mmol/l cells; P=0.107), higher iMg (1.92 versus 1.80 mmol/l cells; P=0.012), but similar iNa (6.86 versus 6.88 mmol/l cells; P=0.93). In men, iK, iMg and iNa did not differ according to ADD1 genotypes. In men, iK (R2=0.128) increased with age and serum Na+, but decreased with serum total calcium and the daily intake of alcohol. iMg (R2=0.087) decreased with age, but increased with serum total calcium. After adjustment for these covariates (P⩽0.04 for all), findings in men for iK (CC versus T: 85.8 versus 87.3 mmol/l; P=0.14) and iMg (1.91 versus 1.82 mmol/l; P=0.03) remained consistent. In 136 women, none of the phenotype–genotype relations reached significance. Changes in intra-erythrocyte cations in ADD2 1797CC homozygous men might lead to osmotic fragility of erythrocytes, but to what extent they reflect systemic changes or are possibly involved in blood pressure regulation remains unknown.

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Acknowledgements

The Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO) is part of the European Project on Genes in Hypertension (EPOGH), which is endorsed by the European Council for Cardiovascular Research and the European Society of Hypertension. FLEMENGHO would not have been possible without the voluntary collaboration of participants and their general practitioners. The municipality Hechtel-Eksel (Belgium) gave logistic support. Research included in the present study was partially funded by the European Union (Grants IC15-CT98-0329-EPOGH and QLGI-CT-2000-01137-EURNETGEN), the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (Grants G.0424.03 and G.0575.06), the Katholieke Universiteit Leuven, Leuven, Belgium (Grants OT/99/28, OT/00/25 and OT/05/49). We gratefully acknowledge the technical assistance of Tamara Coenen, Sandra Covens, Marie-Jeanne Jehoul, Lieve Lommelen, Yvette Piccart, Hanne Truyens, Katrien Staessen and Renilde Wolfs (Studies Coordinating Centre, Leuven, Belgium).

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Authors and Affiliations

  1. Division of Hypertension and Cardiovascular Rehabilitation, Department of Cardiovascular Diseases, Studies Coordinating Centre, University of Leuven, Leuven, Belgium

    T Richart, L Thijs, T Kuznetsova, V Tikhonoff, P Lijnen, R Fagard & J A Staessen

  2. Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy

    V Tikhonoff

  3. Division of Nephrology, D,

    L Zagato & G Bianchi

  4. i,

    L Zagato & G Bianchi

  5. alysis and Hypertension, University Vita Salute San Raffaele, Milan, Italy

    L Zagato & G Bianchi

  6. Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai,, China

    J Wang

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  1. T Richart
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Correspondence to J A Staessen.

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Richart, T., Thijs, L., Kuznetsova, T. et al. Intra-erythrocyte cation concentrations in relation to the C1797T β-adducin polymorphism in a general population. J Hum Hypertens 21, 387–392 (2007). https://doi.org/10.1038/sj.jhh.1002154

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