Impact of mineralocorticoid receptor polymorphisms on urinary electrolyte excretion with and without diuretic drugs
Polymorphisms in the mineralocorticoid receptor may affect urinary sodium and potassium excretion. We investigated polymorphisms in the MR gene in relation to urinary electrolyte excretion in two separate studies. The genotype-phenotype association was studied in healthy volunteers after single doses of bumetanide, furosemide, torsemide, hydrochlorothiazide, triamterene and after NaCl restriction. High potassium excretion under all conditions except torsemide, and high NaCl excretion after bumetanide and furosemide were associated with the A allele of the intron-3 polymorphism (rs3857080). This polymorphism explained 5-10% of the functional variation and in vitro, rs3857080 affected DNA binding of the transcription factor LHX4. rs3857080 may be a promising new candidate for research in cardiac and renal disorders and on antialdosteronergic drugs like spironolactone..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Pharmacogenomics - 16(2015), 2, Seite 115 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dalila, Nawar [VerfasserIn] |
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| Links: |
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| doi: |
10.2217/pgs.14.163 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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OLC1960943561 |
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| 245 | 1 | 0 | |a Impact of mineralocorticoid receptor polymorphisms on urinary electrolyte excretion with and without diuretic drugs |
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| 520 | |a Polymorphisms in the mineralocorticoid receptor may affect urinary sodium and potassium excretion. We investigated polymorphisms in the MR gene in relation to urinary electrolyte excretion in two separate studies. The genotype-phenotype association was studied in healthy volunteers after single doses of bumetanide, furosemide, torsemide, hydrochlorothiazide, triamterene and after NaCl restriction. High potassium excretion under all conditions except torsemide, and high NaCl excretion after bumetanide and furosemide were associated with the A allele of the intron-3 polymorphism (rs3857080). This polymorphism explained 5-10% of the functional variation and in vitro, rs3857080 affected DNA binding of the transcription factor LHX4. rs3857080 may be a promising new candidate for research in cardiac and renal disorders and on antialdosteronergic drugs like spironolactone. | ||
| 650 | 4 | |a Receptors, Mineralocorticoid - drug effects | |
| 650 | 4 | |a Polymorphism, Single Nucleotide - genetics | |
| 650 | 4 | |a Diuretics - pharmacology | |
| 650 | 4 | |a Sulfonamides - pharmacology | |
| 650 | 4 | |a Bumetanide - pharmacology | |
| 650 | 4 | |a Electrolytes - urine | |
| 650 | 4 | |a Hydrochlorothiazide - pharmacology | |
| 650 | 4 | |a Polymorphism, Genetic - genetics | |
| 650 | 4 | |a Potassium - urine | |
| 650 | 4 | |a Receptors, Mineralocorticoid - genetics | |
| 650 | 4 | |a Triamterene - pharmacology | |
| 650 | 4 | |a Furosemide - pharmacology | |
| 650 | 4 | |a Sodium Chloride - urine | |
| 700 | 1 | |a Brockmöller, Jürgen |4 oth | |
| 700 | 1 | |a Tzvetkov, Mladen Vassilev |4 oth | |
| 700 | 1 | |a Schirmer, Markus |4 oth | |
| 700 | 1 | |a Haubrock, Martin |4 oth | |
| 700 | 1 | |a Vormfelde, Stefan Viktor |4 oth | |
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| 856 | 4 | 1 | |u http://dx.doi.org/10.2217/pgs.14.163 |3 Volltext |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/25616098 |
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