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)

We examined whether the GNAS1 locus, encoding the G(s) protein alpha-subunit (G(s)alpha), is implicated in the genetic causes of essential hypertension. A common silent polymorphism (ATT-->ATC, Ile(131)) was identified in exon 5 of the G(s)alpha gene by single-strand conformation polymorphism analysis and DNA sequencing. This polymorphism consists of the presence (+) or absence (-) of a restriction site for FokI. Only 1 other rare allele was found in the coding region; the high GC content of the 5' noncoding sequence prevented mutation scanning of the promoter region of the gene. There was a significant difference in frequency of the FokI alleles between 268 white hypertensives (FokI+:FokI-, 51%:49%) and a matched group of 231 control subjects (FokI+:FokI-, 58%:42%) (P=0.02). Multiple regression analysis showed that the FokI genotype was independently related to the level of untreated systolic blood pressure in 294 well-characterized white hypertensives (P=0.01) but not in normotensives. The influence of the FokI allele on blood pressure (BP) response to beta-blockade was examined in 114 of the patients randomly assigned to this class of drug. Significant differences in frequency of the FokI allele were observed in the good responders (FokI+:FokI-, 62.5%:37.5%, n=36) versus the poor responders (FokI+:FokI-, 41.7%:58.3%, n=30) after beta-blocker therapy (P=0.02). In a multiple regression analysis, the G(s)alpha genotype was the only independent predictor of BP response. These results suggest that the GNAS1 locus might carry a functional variant that influences BP variation and response to beta-blockade in essential hypertension.
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PMID:Association of the G(s)alpha gene with essential hypertension and response to beta-blockade. 1040 16

The natriuretic peptide (NP) family is involved in regulation of blood pressure and fluid volume. We recently characterized the exon/intron organization of the human type A NP receptor (hNPRA) gene. The aim of this study was to isolate the genetic markers according to the organization of this gene, and to study the association between this gene and essential hypertension. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, we identified a novel missense mutation, M3411, consisting of a methionine (ATG) to isoleucine (ATC) substitution at nucleotide 1023 in exon 3. Computer-aided three-dimensional structural analysis suggested that M341 exists in the loop between two alpha-helices, and that the mutation may influence receptor activities by altering the conformation of the alpha-helices. We performed an association study of the mutation in 210 essential hypertension (EH) patients and 210 normotensive controls. The overall distribution of alleles was not significantly different between the control and EH groups. However, the C/C homozygous genotype was found only in the EH group. The ratio of plasma brain natriuretic peptide (BNP)/mean blood pressure of the C/C genotype was significantly higher than that of the G/G genotype or the G/C genotype. We conclude that the significance of homozygous M3411 mutation in exon 3 is worth investigating for its possible association with EH.
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PMID:A novel missense mutation of exon 3 in the type A human natriuretic peptide receptor gene: possible association with essential hypertension. 1213 18