Apolipoprotein E polymorphism modulation of asymmetric dimethylarginine in hypertensive patients is determined by renal function

• Autor(a) principal: Marrocos, Mauro Sergio Martins [UNIFESP]
• Data de Publicação: 2016
• Outros Autores: Teixeira, Andrei Alkmin [UNIFESP], Quinto, Beata Marie [UNIFESP], Carmona, Silmara de Melo [UNIFESP], Kuniyoshi, Mariana [UNIFESP], Rodrigues, Cassio Jose [UNIFESP], Dalboni, Maria Aparecida [UNIFESP], Manfredi, Silvia [UNIFESP], Canziani, Maria Eugenia [UNIFESP], Batista, Marcelo Costa [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/001300000phzn
• DOI: 10.1186/s12944-016-0182-y
• Texto Completo: https://doi.org/10.1186/s12944-016-0182-y; https://repositorio.unifesp.br/handle/11600/58546
• topic: Asymmetric Dimethylarginine; Apolipoprotein E; Polymorphism; Atherogenesis; Chronic Kidney Disease

Background: Endothelial dysfunction is considered an early step of atherosclerotic vascular disease. Asymmetric dimethylarginine (ADMA), the main endogenous inhibitor of nitric oxide synthase (NOS), plays a critical role in the process of atherosclerosis in a uremic environment. Increased plasma ADMA not only works as a cardiovascular morbidity biomarker but it is also involved in the genesis of atherosclerosis in renal disease. Considering the relationships of apolipoprotein E(ApoE) polymorphism with LDL cholesterol (LDL-C) levels and coronary risk, it is possible that it brings on susceptibility to endothelial dysfunction and atherogenesis seen on uremia. Methods: Six hundred twenty patients were stratified according to glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) formula: group I > 60 mL/min, group II <= 60 mL/min and > 15 mL/min, and group III <= 15 mL/min or in hemodialysis. Polymorphic ApoE analysis was performed by polymerase chain reaction amplification (PCR). Plasma ADMA levels were measured by high performance liquid chromatography (HPLC). Groups were compared on clinical and laboratory characteristics as well as allele and genotype distribution towards. Results: The epsilon 2 allele of ApoE was present in 62 (10.3 %) patients, epsilon 3 allele in 581 (96.2 %), and epsilon 4 allele in 114 (18.9 %). Their distribution among the 3 groups was uniform. Such uniformity was not observed when we considered endothelial function measured by asymmetric dimethylarginine. In group III, the frequency of epsilon 4 allele was significantly lower in the third tertile compared with the first tertile (14.7 versus 53.3 %, P = 0.000; Pearson chisquare). In groups I and II, there was no difference in allele frequency according to ADMA levels. This association remained significant even after confouding factors corrections (OR 0.329, 95 % CI 0.155 - 0.699, P = 0.004). Conclusions: The results of this study shows that the frequency of epsilon 4 allele of ApoE is significantly lower among hypertensive patients on hemodialysis with the highest levels of ADMA. Uremia is capable of determining lower plasma ADMA levels in hypertensive epsilon 4 allele carriers.