Abstract 228: Apolipoprotein E (ApoE) Genetic Polymorphism Modulation Of Endothelial Dysfunction In Hypertensive Patients Is Determined By Renal Function.
INTRODUCTION: ADMA, an endogenous inhibitor of nitric oxide synthase, is an independent marker of progression of renal dysfunction, vascular complications and death. Overexpression of the ADMA degrading enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) ameliorates atherosclerosis in genetic ApoE deficient mice. Once ApoE polymorphism is a key player on lipid metabolism, it is possible that it brings on individual susceptibility to endothelial dysfunction.
OBJECTIVE: The aim of this study was to assess the effect of the ApoE genetic polymorphism on ADMA levels in a cohort of hypertensive patients stratified by renal function.
PATIENTS AND METHODS: Patients were stratified into 3 groups according to GFR using the CKD-EPI: I > 60ml/min, II ≤ 60 ml/min and > 15 ml/min, and III ≤ 15 ml/min. HPLC was used for the measurement of ADMA. Polymorphic ApoE analysis performed by PCR amplification and allele frequency compared in each group between first and third tertile of ADMA as epidemiological, clinical and laboratorial characteristics. Statistical analysis performed using the software IBM SPSS Statistics 20.0.
RESULTS: Mean age of the patients was 60.1± 14.1 years, 318 (50.7%) were male, mean BMI was 28.0 ± 5.3, 396 (63.2%) were Caucasians, 244 (38.9%) had DM, 316 (50.4%) had dyslipidemia, 223 (35.6%) had cardiovascular disease (CVD). Groups were composed respectively of 189, 229 and 202 patients. E2 allele was present in 67 (10.7%) patients, E3 allele in 588 (93.8%), E4 allele in 116 (18.5%). In group III, the frequency of E4 allele of ApoE was lower in the third tertile of ADMA (p = .000, Pearson Chi-Square). This link remained significant even after control for confounders like age, sex, BMI, DM, CVD, PCR and LDL (OR 0.127, CI: 0.35 - 0.468, p = .002).
CONCLUSION: ApoE E4 allele independent association with lower levels of ADMA is pronounced among those patients with advanced stage of renal disease. This association may represent an unknown genetic pathway that modulates ADMA levels on this population.
Author Disclosures: M.S.M. Marrocos: None. A.A. Teixeira: None. B.M.R. Quinto: None. C.J. Rodrigues: None. M.A. Dalboni: None. S. Manfredi: None. M.E. Canziani: None. M.C. Batista: None.
- © 2014 by American Heart Association, Inc.