[PP.07.34] GENETIC VARIANT OF ANGIOTENSIN IV RECEPTOR (AT4) AND PLASMA ANGIOTENSIN II CONCENTRATION. (September 2017)

• Record Type: Journal Article
• Authors: Konoshita, T.; Kaeriyama, S.; Urabe, M.; 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 35(2017)Supplement 2
• Publication Date: 2017-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000523387.81474.55
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: It is well known that the renin angiotensin system (RAS) plays a pivotal role in the development of cardiovascular, renal and metabolic conditions. Angiotensin IV receptor (AT4) is a newly emerging component of the RAS. AT4 is a membrane type aminopeptidase and also designated as LNPEP. Actually AT4 converts angiotensin III to angiotensin IV and to further degraded fragments. Thus it is thought that AT4 exerts the enzyme action for the direction of the reduction of angiotensin II. We therefore tested the hypothesis that genetic variants of AT4 could show significant effects on plasma angiotensin II concentrations. Design and method: The required sample size of the study was calculated as about 500 cases tentatively with log-transformed plasma angiotensin II concentrations using a bilateral ANOVA with protection against type I error of 5% and 80% of power. We enrolled consecutive 692 subjects who had consulted our hospitals for life style related diseases. Genomic DNA was isolated from human leukocytes by QIAamp kit. Genotypes were assayed with genomic DNA for a C/T variant of AT4 (rs2303138) using real-time PCR system by TaqMan method. The statistical differences of plasma angiotensin II concentrations among the genetic variants were evaluated. Results: The log-transformed concentrations (log (plasma angiotensin II+1)) with each genotype of AT4 were as follows: CC (260 cases) 0.98 ± 0.48, CT (325 cases) 0.834 ± 0.43, TT (107 cases) 0.78 ± 0.39 (CC vs CT, p = 0.0001; CC vs TT, p < 0.0001; CT vs TT, p = 0.25). Geometric means of these values correspond to 8.51 pg/ml, 5.82 pg/ml and 4.98 pg/ml, respectively. Conclusions: Thus, it is found that a genetic variant of AT4 may have a significant impact on the plasma angiotensin II concentrations. Furthermore this may imply that the genetic variant has pathophysiological effects on cardiovascular, renal and metabolic conditions.