Description:
<jats:p>
<jats:italic>Abstract</jats:italic>
—We examined whether the GNAS1 locus, encoding the G
<jats:sub>s</jats:sub>
protein α-subunit (G
<jats:sub>s</jats:sub>
α), is implicated in the genetic causes of essential hypertension. A common silent polymorphism (ATT→ATC, Ile
<jats:sup>131</jats:sup>
) was identified in exon 5 of the G
<jats:sub>s</jats:sub>
α gene by single-strand conformation polymorphism analysis and DNA sequencing. This polymorphism consists of the presence (+) or absence (−) of a restriction site for
<jats:italic>Fok</jats:italic>
I. 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
<jats:italic>Fok</jats:italic>
I alleles between 268 white hypertensives (
<jats:italic>Fok</jats:italic>
I+:
<jats:italic>Fok</jats:italic>
I−, 51%:49%) and a matched group of 231 control subjects (
<jats:italic>Fok</jats:italic>
I+:
<jats:italic>Fok</jats:italic>
I−, 58%:42%) (
<jats:italic>P</jats:italic>
=0.02). Multiple regression analysis showed that the
<jats:italic>Fok</jats:italic>
I genotype was independently related to the level of untreated systolic blood pressure in 294 well-characterized white hypertensives (
<jats:italic>P</jats:italic>
=0.01) but not in normotensives. The influence of the
<jats:italic>Fok</jats:italic>
I allele on blood pressure (BP) response to β-blockade was examined in 114 of the patients randomly assigned to this class of drug. Significant differences in frequency of the
<jats:italic>Fok</jats:italic>
I allele were observed in the good responders (
<jats:italic>Fok</jats:italic>
I+:
<jats:italic>Fok</jats:italic>
I−, 62.5%:37.5%, n=36) versus the poor responders (
<jats:italic>Fok</jats:italic>
I+:
<jats:italic>Fok</jats:italic>
I−, 41.7%:58.3%, n=30) after β-blocker therapy (
<jats:italic>P</jats:italic>
=0.02). In a multiple regression analysis, the G
<jats:sub>s</jats:sub>
α genotype was the only independent predictor of BP response. These results suggest that the
<jats:italic>GNAS</jats:italic>
1 locus might carry a functional variant that influences BP variation and response to β-blockade in essential hypertension.
</jats:p>