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

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 ε2 allele of ApoE was present in 62 (10.3 %) patients, ε3 allele in 581 (96.2 %), and ε4 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 ε4 allele was significantly lower in the third tertile compared with the first tertile (14.7 versus 53.3 %, P = 0.000; Pearson chi-square). 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 ε4 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 ε4 allele carriers.

Diversity of apolipoprotein E genetic polymorphism significance on cardiovascular risk is determined by the presence of metabolic syndrome among hypertensive patients.

BACKGROUND: Hypertension has a significant relevance as a cardiovascular risk factor. A consistent increase on world's Metabolic Syndrome (MetS) incidence has been associated with an epidemic cardiovascular risk in different populations. Dislipidemia plays a major role determining the epidemic CV burden attributed to MetS. Apolipoprotein E (ApoE) is involved on cholesterol and triglycerides metabolism regulation. Once ApoE polymorphism may influence lipid metabolism, it is possible that it brings on individual susceptibility consequences for the development of MetS and cardiovascular risk. The objective of the study is to measure the discriminatory power of ApoE polymorphism in determining cardiovascular risk stratification based on the presence MetS in a cohort of hypertensive patients. METHODS: It was enrolled 383 patients, divided in two groups, classified by MetS presence (IDF criteria): Group 1: 266 patients with MetS (MetS +) and Group 2: 117 patients without Mets (MetS -). Patient's data were collected by clinical evaluation, physical exam, file reviews and laboratory testing. Polymorphic ApoE analysis was performed by PCR amplification. Groups were compared on clinical and laboratory characteristics as well as allele and genotype distribution towards ApoE polymorphism. Mets CVD prevalence was analysed according to E4 allele prevalence. RESULTS: The results evidenced 184 men (48%), 63,7% whites, 45,1% diabetics and 11,7% of patients were smokers. Mean age was 64,0 ± 12,0 years. When genotypic distribution was analyzed, E3/3 genotype and E3 allele frequencies were more prevalent. Among patients with MetS, we observed an independent association between CVD prevalence and E4 allele frequency (OR 2.42 (1.17- 5.0, p < 0,05)). On the opposite direction, in those without MetS, there was lesser CVD burden in E4 allele carriers (OR 0,14 (0,02-0,75)). These associations remained significant even after confounding factor corrections. CONCLUSIONS: The results presented demonstrate that the association between ApoE gene and CVD may be modulated by the presence of MetS, with an increased CV burden observed among E4 allele carriers with the syndrome. On the opposite way, E4 allele carriers without visceral obesity had lesser prevalence of CVD.