Human G-protein  3 subunit variant is associated with serum potassium and total cholesterol levels but not with blood pressure

Abstract

The activity of a sodium-proton exchanger is enhanced in the patients with essential hypertension and regulated via G-protein, which is a signal transducer between receptors and intracellular effectors. A recent study has revealed that a novel variant (C825T) in exon 10 of the gene encoding the beta3 subunit of heterotrimetric G proteins (GNB3) is a genetic factor predisposing to hypertension in Caucasians. We examined the association between GNB3/ C825T and blood pressure, lipids, electrolytes, and other parameters in a Japanese population. Subjects (n = 352) were selected from the Ohasama Study, the population of which is regarded as from a rural community in Japan. To obtain precise clinical measurements, 24-h ambulatory blood pressure monitoring (ABPM), brain magnetic resonance imaging (MRI), and carotid ultrasonography (CUS) were conducted in this population. In addition, we recruited 762 subjects from outpatients at the Osaka University Medical School to carry out the association study between hypertension and GNB3. The GNB3 genotype distribution did not differ significantly between normotensives and hypertensives in either of the two studies. The T825 allele of GNB3 was not associated with the presence of hypertension, blood pressure level, the number of brain lacunae or carotid wall thickness. However, the serum potassium and total cholesterol levels were significantly higher in subjects with the T allele (P < .005). The T825 allele of GNB3 is associated with increased serum potassium and total cholesterol levels but not with blood pressure in a Japanese population.

Lack of association between the C825T polymorphism in G-protein beta-3 subunit and arterial blood pressure levels in cardiovascular disease free individuals: the ATTICA epidemiological study

“…Several investigators have issued several nongenetic factors as predictors of hypertension status, like obesity, smoking habits, nutritional habits, physical activity and psychological status. [1][2][3][4][5][6][7] The results from our analysis remained similar, after controlling for several of the aforementioned factors, which enhance the eligibility of our reports.…”

“…However, there are other studies that have failed to show significant results regarding the relationship between the polymorphism C825T in the GNB3 gene and blood pressure levels. [5][6][7] Therefore, we sought to evaluate the relationship between the C825T polymorphism in the GNB3 gene with the levels of blood pressure, and the prevalence of hypertension, in a Greek population-based sample of adults.…”

Ambulatory blood pressure and left ventricular structure and function in relation to the G-protein β3-subunit polymorphism C825T in White Europeans

“…47 These discordant findings suggest that ethnic or genetic background, 8 lifestyle or various environmental factors may modulate the potential effect of the C825T allele on blood pressure. The frequency of the T allele was 0.32 in our Caucasian populations, but it is approximately 0.50 in Japanese 45,46 or native Americans 48,49 and 0.75 42,46 in black populations. One possible mechanism for the higher systolic blood pressure might be chronic sodium retention and expansion of the circulating volume as a consequence of the higher activity of the Na + /H + exchanger.…”

“…36 Published studies on the possible influence of the GNB3 C825T polymorphism reported inconsistent results. The 825T allele was associated with increased blood pressure [40][41][42] or increased risk of hypertension 22,43,44 in Germans, 22,39,42,44 Australian White hypertensive patients 41 and Caribbean or West African Blacks, 43 but not in French, 22 Irish, 22 Japanese 45,46 or African Americans. 47 These discordant findings suggest that ethnic or genetic background, 8 lifestyle or various environmental factors may modulate the potential effect of the C825T allele on blood pressure.…”

“…However, in the present study, end-diastolic left ventricular diameter did not increase with the number of T alleles as one might expect in the case of a volume-dependent rise in systolic pressure. Discordance among the published reports on hypertension in relation to the C825T polymorphism 22,23,[40][41][42][43][44][45][46][47] might also be because of the large variability in the blood pressure phenotype. Indeed, in most studies it was only measured on a single occasion by conventional sphygmomanometry.…”