Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type II, to chromosomes 1q31-42 and 17p11-q21 (original) (raw)

Nature Genetics volume 16, pages 202–205 (1997)Cite this article

Abstract

Essential hypertension is a common multifactorial trait. The molecular basis of a number of rare diseases that alter blood pressure in humans has been established, identifying pathways that may be involved in more common forms of hypertension1. Pseudohypoaldosteronism type II (PHAII, also known as familial hyperkalaemia and hypertension or Gordon's syndrome; OMIM ♯145260), is characterized by hyperkalaemia despite normal renal glomerular filtration, hypertension and correction of physiologic abnormalities by thiazide diuretics2,3. Mild hyperchloremia, metabolic acidosis and suppressed plasma renin activity are variable associated findings. The pathogenesis of PHAII is unknown, although clinical studies indicate an abnormality in renal ion transport4. As thiazide diuretics are among the most efficacious agents in the treatment of essential hypertension, understanding the pathogenesis of PHAII may be of relevance to more common forms of hypertension. Analysis of linkage in eight PHAII families showing autosomal dominant transmission demonstrates locus heterogeneity of this trait, with a multilocus lod score of 8.1 for linkage of PHAII to chromosomes 1q31–q42 and 17p11–q21. Interestingly, the chromosome-17 locus overlaps a syntenic interval in rat that contains a blood pressure quantitative trait locus (QTL). Our findings provide a first step toward identification of the molecular basis of PHAII.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, 06510, USA
    Traci A. Mansfield, David B. Simon & Richard P. Lifton
  2. Departments of Genetics, Yale University School of Medicine, New Haven, Connecticut, 06510, USA
    Traci A. Mansfield & Richard P. Lifton
  3. Departments of Medicine, Yale University School of Medicine, New Haven, Connecticut, 06510, USA
    David B. Simon, Margaret Bia & Richard P. Lifton
  4. Department of Medicine E', Sheba Medical Center, Tel Aviv University School of Medicine, Tel Hashomer, 52621, Israel
    Zvi Farfel & Haim Mayan
  5. Division of Endocrinology and Metabolism, Brown University School of Medicine, Providence, Rhode Island, 02908, USA
    Joseph R. Tucci
  6. Department ofNephrology, Centre de Research de L'Hotel-Dieu de Quebec, Quebec, Canada
    Marcel Lebe
  7. The Hypertension and Renal Group, 22 Old Short Hills Road, Livingston, New Jersey, 07039, USA
    Michael Gutkin
  8. Division of Endocrinology, Centre Hospitaller Regional et Universitaire de Marseille, Marseille, France
    Bernard Vialettes & Marie A. Christofilis
  9. Third Department of Medicine, University of Helsinki, Helsinki, Finland
    Ritva Kauppinen-Makelin
  10. Department of Genetics, Stanford University School of Medicine, Stanford, California, 94305, USA
    Neil Risch

Authors

  1. Traci A. Mansfield
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  2. David B. Simon
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  3. Zvi Farfel
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  4. Margaret Bia
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  5. Joseph R. Tucci
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  6. Marcel Lebe
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  7. Michael Gutkin
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  8. Bernard Vialettes
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  9. Marie A. Christofilis
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  10. Ritva Kauppinen-Makelin
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  11. Haim Mayan
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  12. Neil Risch
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  13. Richard P. Lifton
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Correspondence toRichard P. Lifton.

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Mansfield, T., Simon, D., Farfel, Z. et al. Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type II, to chromosomes 1q31-42 and 17p11-q21.Nat Genet 16, 202–205 (1997). https://doi.org/10.1038/ng0697-202

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