Abstract
Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of nitric oxide (NO) synthesis, and play a critical role in the process of endothelial dysfunction, and are considered markers of oxidative stress. The aim of the present study was to explore relationships between ADMA and/or SDMA and the occurrence of OSA in obese patients as well as the effect of the endothelial nitric oxide synthase (eNOS) gene polymorphism, which may modify the influence of ADMA or SDMA on NO production. A total of 518 unrelated obese subjects were included in this study. Body weight, height and blood pressure were measured and data on self-reported smoking status were collected. Obstructive sleep apnea (OSA) was assessed by the apnea hypopnea index (AHI). Blood samples were collected to measure serum concentrations of glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, creatinine, HbA1c (%), folic acid, vitamin B12, C-reactive protein (CRP), aspartate aminotransferase (ASP), alanine aminotransferase (ALT) and IL-6 by routine methods. The NOS3 gene G894T and 4a/4b polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. ADMA, SDMA and arginine concentrations were assessed simultaneously using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method. Adjusted multivariate logistic regression analysis showed a significant association between the occurrence of OSA and high serum ADMA levels, BMI above 40, age > 43 years, hypertension and male sex. Heterozygotes for the G894T eNOS polymorphism have the lowest serum concentrations of ADMA and SDMA, while no effect of the 4a/4b variants was observed. The results indicate that OSA in obese individuals can coexist with high ADMA levels, which appear as a potential OSA predictor.
Highlights
Obstructive sleep apnea (OSA) is a chronic, sleep-related breathing disorder with increasing prevalence
Levels of Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were statistically significantly associated with a number of the biomarkers tested (Table 1), with moderate correlations found only between SDMA and creatinine, and estimated glomerular filtration rate (eGFR), with the remaining having weak correlations (i.e., BMI, apnea hypopnea index, folic acid, B12, fat%, C-reactive protein (CRP), interleukine 6 (IL-6), age, HbA1c%, glucose and lipids)
The loss of nitric oxide (NO) production and bioactivity can be associated with development of pathological conditions such as hypertension or obstructive sleep apnea (OSA) [14,15]
Summary
Obstructive sleep apnea (OSA) is a chronic, sleep-related breathing disorder with increasing prevalence. Nitric oxide is involved in many biological processes It causes the relaxation of smooth muscle cells and the subsequent vasodilatation of blood vessels; prevents smooth muscle cells proliferation and migration; reduces platelet adhesion and aggregation; and reduces monocyte stickiness. Clinical and experimental evidence indicate that ADMA and SDMA are involved in the endothelial dysfunction, oxidative stress, and inflammation [6,7] and are associated with an enhanced risk of cardiovascular diseases [2,4,8]. The aim of the present study was to explore relationships between the occurrence of OSA in individuals with obesity and ADMA and/or SDMA levels, as well as the effect of the endothelial nitric oxide synthase (eNOS) gene polymorphism, which may modify the influence of ADMA or SDMA on NO production
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