2019 Volume 43 Issue 1 Pages 11-17
Uric acid is considered to be one of the risk factors for atherosclerotic disorders. The suggested mechanisms include renin angiotensin system (RAS) activation. It is well-known that RAS plays a pivotal role in atherosclerotic disorders. However, evidence that uric acid is involved in RAS activation is still not sufficient. We therefore tested the hypothesis that a genetic variant of a uric acid transporter, SLC2A9 (GLUT9), was significantly correlated with the prevalence of a hyper-reninemic state. We enrolled 804 consecutive patients who had consulted our hospitals for lifestyle-related diseases. We divided them into a hyper-reninemic group as cases and normo-reninemic group as controls based on plasma renin activity (PRA). Genomic DNA was isolated from leukocytes. Genotypes were assayed for C/Tvariants using the real-time PCR system with the TaqMan method. The association between genetic variants and the hyper-reninemic state was tested. Compared with the CC and CT groups, the serum uric acid level of the TT group was significantly higher. Accordingly, the risk of a hyper-reninemic state was around 1.2 for the T allele, with significance on allelic comparison. Armitage’s trend test also revealed that the T allele was the risk allele. The uric acid levels are associated with a genetic variant of GLUT9, and subjects with the high uric acid variant show a hyper-reninemic constitution. Thus, from the viewpoint of the Mendelian randomization theory, a high uric acid state may have a significant impact on RAS activation.
