Objectives: Hyperuricemia associates with hypertension, but it is uncertain whether this relationship is causal in nature. Glucose transporter 9 (GLUT9) gene is a major genetic determinant of plasma uric acid levels in humans. Since polymorphisms are randomly distributed at mating (Mendelian randomization), studies based on GLUT9 polymorphisms may provide unconfounded assessment of the nature of the link between uric acid and hypertension.
Methods: We tested the association between uric acid, the rs734555 polymorphism of the GLUT9 gene and arterial pressure in a family-based study including 449 individuals in a genetically homogenous population in Southern Italy.
Results: Serum uric acid levels were strongly associated (P < 0.001) with all components of clinic and 24-h ambulatory blood pressures (BPs). However, only clinic SBP and the white-coat effect (the difference in clinic systolic and daytime systolic ambulatory blood pressure monitoring) associations remained significant after adjustment for classical risk factor and the estimated glomerular filtration rate. Serum uric acid was strongly associated with the risk allele (T) of the rs734555 polymorphism (P < 0.001). Furthermore, TT individuals showed higher clinic SBP (129 + SEM 1 mmHg) than GT (125 + 1 mmHg) and GG individuals (122 + 3 mmHg), as well as a higher white-coat effect (P = 0.02), confirming that the association between uric acid and these BP components is unconfounded by environmental risk factors.
Conclusion: Results in this family-based study are compatible with the hypothesis that uric acid is a causal risk factor for hypertension. Trials testing uric acid-lowering interventions are needed to definitively establish the causal implication of hyperuricemia in human hypertension.
aCNR-IBIM, Reggio Calabria
bUnità Operativa di Nefrologia, Ipertensione e Trapianto Renale Ospedali Riuniti, Reggio Calabria, Italy
Correspondence to Professor Carmine Zoccali, CNR-IBIM & Divisione di Nefrologia e Dialisi, c/o euroline di barilla’ francesca, Via Vallone Petrara 55–57, 89124 Reggio Calabria, Italy. Tel: +39 0965 397010; fax: +39 0965 26879; e-mail: firstname.lastname@example.org
Abbreviations: ABPM, ambulatory blood pressure monitoring; BP, blood pressure; eGFR, estimated glomerular filtration rate; GLUT9, glucose transporter 9; PRA, plasma renin activity; SNP, single-nucleotide polymorphism
Received 27 December, 2013
Revised 26 March, 2014
Accepted 26 March, 2014