Association of RASGRP1 Polymorphism with Vascular Complications in Chinese Diabetic Patients with Glycemic Control and Antihypertensive Treatment

Abstract

Background: Studies have shown that RASGRP1 was strongly associated with the onset of type 2 diabetes, and RASGRP1 rs7403531 was significantly correlated with islet function in type 2 diabetes (T2DM) patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment is still unclear. Methods: We retrospectively analyzed a large multicenter drug clinical study cohort that based on a 2×2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, and follow-up for 5 years. The major vascular endpoint events in our study included cardiovascular death, non-fatal stroke, coronary heart disease, new or worsening kidney disease, and diabetic retinopathy. Mixed linear model and Cox hazard ratio model were used for data analysis with SPSS. Findings: A total of 1357 patients were included in our research with an average follow-up time of 4.8 years. RASGRP1 rs7403531 T allele could reduce the risk of major microvascular events (HR=0.41, 55%CI 0.21-0.80, P =0.009) and major eye diseases(HR=0.44, 95% CI 0.20-0.94, P =0.03) in T2DM patients . In the group based on antihypertensive therapy, active antihypertensive therapy for CC patients reduced the risk of all cerebrovascular events (placebo vs. antihypertensive: HR=2.35, 95% CI 1.06-5.12, P =0.035). For RASGRP1 (rs56254815), compared with the AA genotype carriers, the SBP of AG/GG carriers in the hypotensive group decreased by 1.5mmhg on average ( P =0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers ( P =0.02). Interpretation: Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients. Trial Registration: (Registration number NCT00145925). Funding Statement: Supported by the National Natural Science Foundation of China (NSFC, No 81573511, 81874329, 81522048), the National Key R&D Plan of China (No. 2016YFC0905000). Declaration of Interests: All authors declare no conflict of interest relevant to the subject matter or materials discussed in the article. Ethics Approval Statement: Approval to conduct the trial was obtained from the ethics committee of each study center, and all participants provided written informed consent.