Healthy Subjects Carrying the G Protein β3 Subunit 825T-Allele Exhibit Higher Uric Acid Serum Levels

Introduction

The association between hypertension, central obesity, insulin resistance, and dyslipidemia has long been recognized, and is now known as ‘metabolic syndrome’. An elevation in uric acid has consistently been described in patients with this syndrome [1], and it has been shown to increase blood pressure in one experimental animal model [2]. Multiple epidemiological and pathogenetic links exist between metabolic syndrome and hyperuricemia, and their prevalence is strongly influenced by genetic factors [3]. This suggests that they may share a common genetic background. Indeed, an association between the T-allele of the C825T polymorphism in the gene encoding the β3 subunit of heterotrimeric G-proteins (GNB3) has been described for both hypertension [4] [5] [6] and obesity [7] [8]. Recently, the association between the 825T-allele and hypertension has been further confirmed in Japanese subjects [9].

In order to explore any potential genetic link between hypertension and disturbances in lipids, glucose and uric acid metabolism further, we compared fasting serum levels of lipids, glucose, and uric acid in young, healthy males with and without the 825T-allele. A reciprocal pathogenetic relationship between elevation in blood pressure, body weight, lipids, glucose and uric acid has been established. According to Selby et al., serum uric acid is closely linked to the development of hypertension, and may be a marker of susceptibility leading to hypertension [10]. Therefore, we deliberately confined our analysis to young subjects with normal blood pressure who were not obese (defined as body mass index BMI < 29.9 kg/m²). Since both hypertension and obesity as two hallmarks of metabolic syndrome are at least partly determined by the polymorphism in the GNB3 gene, we hypothesized that young, healthy carriers of the 825T-allele would also show elevated serum lipid, glucose or uric acid levels compared to subjects with the CC genotype.

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