Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA) Concentrations in Patients with Obesity and the Risk of Obstructive Sleep Apnea (OSA)
Asymmetric Dimethylarginine (ADMA) and Symmetric Dimethylarginine (SDMA) Concentrations in Patients with Obesity and the Risk of Obstructive Sleep Apnea (OSA)
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DOI：
10.3390/jcm8060897
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发表时间：
2019-06-01
影响因子：
3.9
通讯作者：
Wrzosek, Malgorzata
中科院分区：
文献类型：
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作者：
Arlouskaya, Yana;Sawicka, Ada;Wrzosek, Malgorzata
不对称二甲基精氨酸（ADMA）和对称二甲基精氨酸（SDMA）是一氧化氮（NO）合成的内源性抑制剂，在内皮功能障碍过程中发挥关键作用，被认为是氧化应激的标志物。本研究的目的是探讨 ADMA 和/或 SDMA 与肥胖患者 OSA 发生之间的关系以及内皮型一氧化氮合酶 (eNOS) 基因多态性的影响，这可能会改变 ADMA 或 SDMA 对 NO 产生的影响。本研究共纳入 518 名不相关的肥胖受试者。测量体重、身高和血压，并收集自我报告的吸烟状况数据。阻塞性睡眠呼吸暂停（OSA）通过呼吸暂停低通气指数（AHI）进行评估。采集血样，按常规方法测定血清葡萄糖、总胆固醇、LDL-胆固醇、HDL-胆固醇、甘油三酯、肌酐、HbA1c(%)、叶酸、维生素B-12、C反应蛋白(CRP)、天冬氨酸转氨酶(ASP)、丙氨酸转氨酶(ALT)和IL-6浓度。采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)分析检测NOS3基因G894T和4a/4b多态性。使用液相色谱串联质谱 (LC-MS/MS) 方法同时评估 ADMA、SDMA 和精氨酸浓度。调整后的多变量逻辑回归分析显示，OSA 的发生与高血清 ADMA 水平、BMI 高于 40、年龄 > 43 岁、高血压和男性之间存在显着相关性。 G894T eNOS 多态性杂合子的 ADMA 和 SDMA 血清浓度最低，而没有观察到 4a/4b 变体的影响。结果表明，肥胖个体的 OSA 可以与高 ADMA 水平共存，这似乎是潜在的 OSA 预测因子。
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 B-12, 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.