Arlouskaya Yana, Sawicka Ada, Głowala Marek, Giebułtowicz Joanna, Korytowska Natalia, Tałałaj Marek, Nowicka Grażyna, Wrzosek Małgorzata
Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy and Laboratory of Biochemistry and Clinical Chemistry at the Preclinical Research Center, Medical University of Warsaw, 02-097 Warsaw, Poland.
Department of Family Medicine, Internal Medicine and Metabolic Bone Diseases, Medical Centre of Postgraduate Education, 00-416 Warsaw, Poland.
J Clin Med. 2019 Jun 23;8(6):897. doi: 10.3390/jcm8060897.
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, C-reactive protein (CRP), aspartate aminotransferase (ASP), alanine aminotransferase (ALT) and IL-6 by routine methods. The 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.
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起关键作用,被视为氧化应激的标志物。本研究的目的是探讨ADMA和/或SDMA与肥胖患者阻塞性睡眠呼吸暂停(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,该基因多态性可能会改变ADMA或SDMA对NO产生的影响。本研究共纳入518名无亲属关系的肥胖受试者。测量体重、身高和血压,并收集自我报告的吸烟状况数据。通过呼吸暂停低通气指数(AHI)评估阻塞性睡眠呼吸暂停(OSA)。采集血样,采用常规方法测量血清葡萄糖、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯、肌酐、糖化血红蛋白(HbA1c,%)、叶酸、维生素B、C反应蛋白(CRP)、天冬氨酸转氨酶(ASP)、丙氨酸转氨酶(ALT)和白细胞介素-6的浓度。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析检测基因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。校正后的多因素逻辑回归分析显示,OSA的发生与高血清ADMA水平、BMI高于40、年龄>43岁、高血压和男性性别之间存在显著关联。G894T eNOS基因多态性的杂合子血清ADMA和SDMA浓度最低,而未观察到4a/4b变异体的影响。结果表明,肥胖个体中的OSA可能与高ADMA水平共存,高ADMA水平似乎是OSA的一个潜在预测指标。