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. 2016 Jan 20:15:14.
doi: 10.1186/s12944-016-0182-y.

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

Mauro Sergio Martins Marrocos  1 , Andrei Alkmin Teixeira  2 , Beata Marie Quinto  3 , Silmara de Melo Carmona  4 , Mariana Kuniyoshi  5 , Cassio Jose Rodrigues  6 , Maria Aparecida Dalboni  7 , Silvia Manfredi  8 , Maria Eugênia Canziani  9 , Marcelo Costa Batista  10   11   12
Affiliations

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

Mauro Sergio Martins Marrocos et al. Lipids Health Dis. .

Abstract

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.

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Figures

Fig. 1
Fig. 1
Comparison of frequency of ApoE ε4 allele between ADMA tertiles 3 and 1 in renal function groups
See this image and copyright information in PMC

References

    1. Saran R, Li Y, Robinson B, Ayanian J, Balkrishnan R, Bragg-Gresham J, et al. U S renal data system 2014 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis. 2015;65(6 Suppl 1):S1–S306. - PMC - PubMed
    1. Leone A, Moncada S, Vallance P, Calver A, Collier J. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet. 1992;339:572–575. doi: 10.1016/0140-6736(92)90865-Z. - DOI - PubMed
    1. Kielstein JT, Frölich JC, Haller H, Fliser D. ADMA (asymmetric dimethylarginine): an atherosclerotic disease mediating agent in patients with renal disease? Nephrol Dial Transplant. 2001;16:1742–1745. doi: 10.1093/ndt/16.9.1742. - DOI - PubMed
    1. Kajimoto H, Kai H, Aoki H, Yasuoka S, Anegawa T, Aoki Y, et al. Inhibition of eNOS phosphorylation mediates endothelial dysfunction in renal failure: new effect of asymmetric dimethylarginine. Kidney Int. 2012;81:762–768. doi: 10.1038/ki.2011.476. - DOI - PubMed
    1. Lu TM, Chung MY, Lin CC, Hsu CP, Lin SJ. Asymmetric dimethylarginine and clinical outcomes in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6:1566–1572. doi: 10.2215/CJN.08490910. - DOI - PubMed

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