Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension

Hannila‐Handelberg, Tuula; Kontula, Kimmo; Tikkanen, Ilkka; Tikkanen, Tuula; Fyhrquist, Frej; Helin, Kristian; Fodstad, Heidi; Piippo, Kirsi; Miettinen, Helena E.; Virtamo, Jarmo; Krusius, Tom; Sarna, Seppo; Gautschi, Ivan; Schild, Laurent; Hiltunen, Timo P.

doi:10.1186/1471-2350-6-4

Cited by 55 publications

(41 citation statements)

References 38 publications

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“…The recruitment and characteristics of referred hypertensive patients have been described previously. 15 In brief, patients referred to the Hypertension Outpatient Ward of Helsinki University Central Hospital because of hypertension resistant to drug treatment were studied. Secondary hypertension was excluded with appropriate clinical and laboratory examinations.…”

Section: Methods Subjectsmentioning

confidence: 99%

STK39 variation predicts the ambulatory blood pressure response to losartan in hypertensive men

et al. 2011

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Large-scale genome-wide association studies (GWASs) have identified significant associations of common genetic variants with blood pressure (BP) levels. To obtain more evidence for the role of these variants in BP regulation, we studied their association with BP responses to four different antihypertensive drug monotherapies. We selected 19 single-nucleotide variants based on data from five GWASs. The study group consisted of more than 200 hypertensive Finnish men from the GENRES study. Ambulatory BP responses to 4-week treatments with losartan, bisoprolol, hydrochlorothiazide and amlodipine were the primary targets of the study. Secondarily, baseline indicators of the activity of the renin-angiotensin-aldosterone system were studied. After correction for multiple comparisons, the variant rs6749447 in the STK39 gene was significantly associated with BP responses. Thus, the minor rs6749447 allele was associated with a lower systolic and diastolic BP response to losartan (P¼0.0005 and 0.0002, respectively). rs6749447 minor allele homozygotes had marginally higher serum aldosterone/plasma renin activity (PRA) ratios (P¼0.04) than those without this allele. In a replication study on aldosterone and renin levels, another cohort of hypertensive patients (n¼311) showed a similar trend. When the two cohorts were combined, the aldosterone level (P¼0.02) and the aldosterone/PRA ratio (P¼0.01) were higher in subjects homozygous for the minor rs6749447 allele than in other subjects. The present study shows that pharmacogenetic approaches may provide evidence that complements systematic genome-wide strategies by identifying gene loci that not only affect the BP level but also might modify its response to pharmacologic interventions.

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Section: Methods Subjectsmentioning

confidence: 99%

STK39 variation predicts the ambulatory blood pressure response to losartan in hypertensive men

et al. 2011

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“…Patients with the variant alleles showed an increased urinary potassium excretion rate in relation to their renin levels. 41 No increase in channel activity could be detected when these ENaC variants were expressed in Xenopus oocytes. Thus, the functional relevance of these variants remains uncertain.…”

Section: ␤Enacmentioning

confidence: 99%

“…41 At least 9% of Finnish patients with hypertension, admitted to a specialized center, carry genetic variants of ␤ENaC and ␥ENaC, a 3ϫ higher prevalence than in the normotensive individuals or in random healthy controls. Patients with the variant alleles showed an increased urinary potassium excretion rate in relation to their renin levels.…”

Section: ␤Enacmentioning

confidence: 99%

Epithelial Sodium Channel

Rossier

Schild

2008

Hypertension

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“…Gene variants of ENaC (epithelium sodium channel) (Hannila-Handelberg et al, 2005) and of CYP3A5 enzyme (11-hydroxysteroid dehydrogenase type 2) (Givens et al, 2003;Ho et al, 2005) have been demonstrated, focusing attention on sodium homeostasis, and on cortisol and corticosterone metabolism but the clinical relevance of these mutations is unclear.…”

Section: Prevalencementioning

confidence: 99%

Resistant Hypertension, Elevated Aldosterone/Renin Ratio and Reduced RGS2: A Pathogenetic Link Deserving Further Investigations?

Semplicini¹,

Stella²,

Ceolotto³

2012

Genetics and Pathophysiology of Essential Hypertension

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Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension

Abstract: Background: Rare mutations of the epithelial sodium channel (ENaC) result in the monogenic hypertension form of Liddle's syndrome. We decided to screen for common variants in the ENaC βand γ subunits in patients with essential hypertension and to relate their occurrence to the activity

Cited by 55 publications

References 38 publications

STK39 variation predicts the ambulatory blood pressure response to losartan in hypertensive men

STK39 variation predicts the ambulatory blood pressure response to losartan in hypertensive men

Epithelial Sodium Channel

Resistant Hypertension, Elevated Aldosterone/Renin Ratio and Reduced RGS2: A Pathogenetic Link Deserving Further Investigations?

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