Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The "reverse genetic" approach to essential hypertension is complicated by the fact that blood pressure is a heterogeneous, quantitative, complex trait. One strategy is to use "intermediate phenotypes" that are not only associated with hypertension but that also have a simple mode of inheritance, compatible with the action of a single gene. Red cell sodium-lithium countertransport (SLC) is one of the best characterized intermediate phenotypes for hypertension. The similarity in stoichiometry and kinetics between SLC and Na+/H+ exchange has led to the proposal that the gene encoding the Na+/H+ antiporter (APNH) may be responsible for the individual variance in SLC. We have tested this hypothesis by both an association study and Haseman and Elston's sib pair method of linkage analysis, by using a polymorphism at the APNH locus detected by denaturing gradient gel electrophoresis. Both analytical techniques were performed before and after correction of SLC values for known covariates. There was no significant association between mean SLC values and any of the three possible genotypes of the APNH locus either before or after regressing out covariates (F = 0.64 and P greater than 0.52; F = 0.63 and P greater than 0.53, respectively). Linkage analysis similarly failed to demonstrate a relationship between the squared difference in SLC values and the identity by descent status for APNH as well as other loci that map close to APNH (D1S57, RH, and ALPL). Taking these results together, we conclude that mutations at the APNH locus are not responsible for the observed variation in SLC values.
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PMID:Assessing the role of APNH, a gene encoding for a human amiloride-sensitive Na+/H+ antiporter, on the interindividual variation in red cell Na+/Li+ countertransport. 166 Nov 90

The Na+/H+ antiporter is a ubiquitous membrane-associated protein that plays an important role in the regulation of intracellular pH. APNH, a gene encoding the antiporter, has been cloned and mapped to the short arm of chromosome 1 by in situ hybridization. Using the polymerase chain reaction, we have amplified a 376 base pair fragment corresponding to the 5' end of APNH. We have detected a polymorphism within this fragment by denaturing gradient gel electrophoresis. Using polymorphisms at other 1p loci (ALPL, the gene for alkaline phosphatase, RH and D1S57), we have been able to map APNH telomeric to D1S57 and close to RH and ALPL by genetic linkage. APNH is a plausible candidate gene for human essential hypertension; the APNH polymorphism combined with a knowledge of its genetic map location allow this candidate to be tested in hypertensive kindreds and sib-pairs.
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PMID:The Na+/H+ antiporter: a "melt" polymorphism allows regional mapping to the short arm of chromosome 1. 197 10

The aim of this work is to evaluate whether type 2 diabetes mellitus, obesity and arterial hypertension, three conditions characterized by the presence of insulin resistance, share some common genetic markers. A potential candidate is the Na+/H+ antiporter, the increased activity of which is considered a marker of essential hypertension. This ion exchanger seems to be related to the Na+/Li+ countertransport, that is considered a marker of insulin resistance in essential hypertension and in type 1 diabetes mellitus. In this study we wished to clarify whether the activity of the Na+/H+ antiporter is increased not only in hypertensive subjects, but also in obese and type 2 diabetic patients, both in the presence and in the absence of arterial hypertension. The activity of the ion exchanger was measured in peripheral blood lymphocytes (PBL) by clamping intracellular pH (pHi) at 5.8-6.2 and then detecting the rate of the proton efflux after sodium addition. In the absence of arterial hypertension, no significant difference in this parameter was observed in obese and type 2 diabetic patients in comparison with normal subjects. In the presence of arterial hypertension, there was a significant increase in the Na(+)-induced H+ efflux at the internal pH (pHi) values of 5.8 and 6.2 both in hypertensive controls and in hypertensive obese and type 2 diabetic patients (P = 0.05-0.0001 vs. normotensive subjects and patients).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Na+/H+ antiporter activity in peripheral blood lymphocytes of obese and type 2 diabetic patients is increased only in the presence of arterial hypertension. 803 50

Sodium transport including amiloride-sensitive Na+/H+ antiporter activity was measured in cheek epithelial cells of adolescents displaying either high or low BP tracking characteristics and in a subgroup of high BP tracking adolescents exhibiting a positive family history of hypertension. From the BP tracking behaviour of over 500 adolescents measured over a period of three years, 24 low BP tracking and 29 high BP tracking adolescents were recruited for the study. Cheek cells were collected from these subjects and proton-dependent, amiloride-sensitive Na+/H+ antiporter activity and the response of this antiporter to a proton gradient were measured. Cheek cell Na+/H+ antiporter activity was 50% lower (P = 0.0004) in the high BP tracking group (1.02 +/- 0.15 nmol Na+/mg protein/5 min (mean +/- SEM) compared with the activity in the low BP tracking group (2.05 +/- 0.24). A significantly lower Na+/H+ antiporter activity (69%; P < 0.01) was also apparent in the high BP tracking adolescents with family history of hypertension (n = 7) compared with the low BP tracking group. The graded response of cheek cell Na+/H+ antiporter activity to the proton gradient was 58% lower (P = 0.0039) for adolescents in the high BP tracking group compared with the low BP tracking group. Passive Na+ influx was also significantly lower in the cheek cells of the high BP tracking group. Our results therefore show that the activity of the Na+/H+ antiporter in cheek cells and the passive Na+ transport activity are lower in those adolescents considered at greatest risk of future development of essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sodium transport activity in cheek epithelial cells from adolescents at increased risk of hypertension. 806 79

Recent investigations have raised a possibility that abnormal ion transportation through cell membranes may be involved in the pathogenesis of essential hypertension. In order to test the hypothesis that increased activity of Na+/H+ antiporter may cause hypertension, we developed transgenic mice overexpressing the Na+/H+ antiporter. We isolated a full-length cDNA clone encoding the rabbit Na+/H+ antiporter and constructed the transgene by ligating it with the human elongation factor 1 alpha promoter. We obtained three transgenic strains which express the transgene in various tissues such as kidney, heart and aorta. These transgenic mice may be useful for the analysis of pathogenesis of essential hypertension.
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PMID:[Production of transgenic mice overexpressing rabbit Na+/H+ antiporter]. 839 97