ASSOCIATION STUDY OF URIC ACID TRANSPORTER GLUT9 GENOTYPE WITH THE RENIN-ANGIOTENSIN SYSTEM. (June 2018)

• Record Type: Journal Article
• Authors: Konoshita, T.; Urabe, M.; Kaeriyama, S.; Nakaya, T.; Yamada, M.; Ichikawa, M.; Sato, S.; Yamamoto, K.; Imagawa, M.; Fujii, M.; Zenimaru, Y.; Suzuki, J.; Makino, Y.
• Is Part Of: Journal of hypertension. Volume 36(2018)Supplement 1
• Publication Date: 2018-06
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000539181.62214.8a
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Uric acid is thought to be one of risk factors for atherosclerotic disorders. The mechanisms have been thought to include endothelial dysfunction, inflammation, oxidative stress and the renin angiotensin system (RAS) activation. It is known that the RAS plays a pivotal role in the atherosclerotic disorders. However, the evidence that uric acid is involved in the activation is not sufficient. We therefore tested the hypothesis that a genetic variant of a uric acid transporter, glucose transporter 9 (GLUT9) could show significant association with prevalence of hyper-reninemic state. Design and method: We enrolled consecutive 804 subjects who had consulted our hospitals for life style related diseases (statistic power 80%, significance level 0.05). We defined the subjects with plasma renin activity (PRA) equal with or more than 0.70 mg/ml/hr. as hyper-reninemic group as cases of the study and the subjects with PRA less than 0.70 mg/ml/hr as normo-reninemic group as controls. Genomic DNA was isolated from human leukocytes. Genotypes were assayed with genomic DNA for a C/T variant of GLUT9 (rs1014290) using real-time PCR system by TaqMan method. Association between the genetic variant and the prevalence of hyper-reninemic state was tested. Results: They consisted of cases (51.0%) and controls (49.0%). The serum uric acid (mg/dl) with each genotype of GLUT9 were as follows: CC (127 cases) 5.04 ± 1.45, CT (392 cases) 5.08 ± 1.49, TT (286 cases) 5.44 ± 1.45 (CC vs CT, p = 0.77; CC vs TT, p = 0.011; CT vs TT, p = 0.002). The numbers of individuals with each genotype were as follows (CC, CT and TT): 52, 204 and 154 for cases and 75, 187 and 132 for controls. Accordingly, the risk for hyper-reninemic state was 1.24 (95% confidence interval; 1.02–1.52), p = 0.033 for allelic comparison and also p = 0.032 for Armitage's trend test, the T allele being the risk allele. Conclusions: The uric acid concentration is associated with a genetic variant of transporter GLUT9 and the subjects with genetic variant of high uric acid have hyper-reninemic constitution. Thus, from a view point of Mendelian randomization theory, it is found that high uric acid state may have a significant impact on the RAS activation.