Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between blood pressure and sodium (Na) excretion is less steep in hypertension caused by increased renal tubular reabsorption. We recently demonstrated that one mutation in rat alpha-adducin gene: (1) is responsible for approximately 50% of the hypertension of MHS rats, and (2) stimulates tubular Na-K pump activity when transfected in renal epithelial cell, suggesting that its pressor effect may occur because an increased tubular reabsorption. Linkage and association studies demonstrated that the alpha-adducin locus is relevant for human hypertension. A point mutation (G460W) was found in human alpha-adducin gene, the 460W variant (G/W) is more frequent in hypertensives than in normotensives. The aim of this study was to test whether acute changes in body Na may differently affect blood pressure in humans as a function of alpha-adducin genotype. The pressure-natriuresis relationship was analyzed in 108 hypertensive using two different acute maneuvers: Na removal (furosemide 25 mg p.o.) and, two days later, Na load (310 mmoles i.v. in 2 hr). We found that 80 patients were wild-type homozygous (G/G), 26 were G/W heterozygous, and 2 were W/W homozygous with similar blood pressure, age body mass index, gender, plasma and urinary sodium and potassium. In basal condition G/W-W/W patients showed a lower plasma renin activity and fractional excretion of Na. In either case the pressure-natriuresis relationship was less sleep in G/W-W/W than in G/G patients, obviously negative for Na depletion with furosemide (-0.011 +/- 0.004 vs. -0.002 +/- 0.002 mm Hg/mumol/min, P < 0.03), and positive for Na load (0.086 +/- 0.02 vs. 0.027 +/- 0.007 mm Hg/mumol/min, P < 0.001). The finding of reduced slope after Na depletion or Na load supports the hypothesis that, as MHS rats, humans bearing one W alpha-adducin variant display an increased of renal tubular sodium reabsorption.
 ...
PMID:Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients. 960 77

The alpha-adducin gene contributes significantly to hypertension in MHS rats (rats of the Milan hypertensive strain) and in some white and Japanese populations, causing a low renin, sodium, and diuretic-sensitive hypertension. No data are available from populations of African ancestry who have a high prevalence of low renin, sodium, and diuretic-sensitive hypertension. We studied the relationship between the 460-Trp variant of alpha-adducin gene with hypertension using a case-control study design in black South Africans. Surprisingly we found that the overall frequency of the 460-Trp allele was low (approximately 6%), but in spite of such relatively low frequency, the 460-Trp allele was 2.5-fold more frequent in hypertensives than normotensives (P = .028), with an odds ratio for hypertension associated to the state of carrier of at least one 460-Trp allele of 2.68. The finding of such low frequency of the 460-Trp allele in individuals of African ancestry points to the substantial ethnic variability of the genes that have been found to be associated with hypertension. On the other hand, it suggests an association of the 460-Trp allele with hypertension also in subjects of African origin.
 ...
PMID:Alpha-adducin polymorphism in hypertensives of South African ancestry. 1091 63

In a previous study, by using a candidate gene approach, we detected in both Milan hypertensive rats and humans a polymorphism in the alpha-adducin gene (ADD1) that was associated with blood pressure and renal sodium handling. In the present study, a genomewide search with 264 informative markers was undertaken in 251 (Milan hypertensive strain x Milan normotensive strain) F2 rats to further investigate the contribution of the adducin gene family (Add1, Add2, and Add3) and to identify novel quantitative trait loci (QTLs) that affect blood pressure. The influence of 2 different methods of blood pressure measurement, the intracarotid catheter and the tail-cuff method, was also evaluated. We found evidence that QTLs affected systolic blood pressure (SBP) measured at the carotid (direct SBP) on rat chromosome 1 with a logarithm of the odds (LOD) score peak of 3.3 on D1Rat121 and on rat chromosome 14 on Add1 locus (LOD=3.2). A QTL for SBP measured at the tail (indirect SBP) was found on rat chromosome 10 around D10Rat33 (LOD=5.0). All of these QTLs identified chromosomal regions not detected in other rat studies and harbor genes (Na(+)/H(+) exchanger A3; alpha-adducin; alpha(1B)-adrenergic receptor) that may be involved in blood pressure regulation. Therefore, these findings may be relevant to human hypertension, also in consideration of the biochemical and pathophysiological similarities between MHS and a subgroup of patients of primary hypertension, which led to the identification of alpha-adducin as a candidate gene in both species.
 ...
PMID:Genetic mapping of blood pressure quantitative trait loci in Milan hypertensive rats. 1108 36