An Ethnic Comparison of Arginine Dimethylation and Cardiometabolic Factors in Healthy Black and White Youth: The ASOS and African-PREDICT Studies
An Ethnic Comparison of Arginine Dimethylation and Cardiometabolic Factors in Healthy Black and White Youth: The ASOS and African-PREDICT Studies
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DOI：
10.3390/jcm9030844
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发表时间：
2020-03-01
影响因子：
3.9
通讯作者：
Tsikas, Dimitrios
中科院分区：
文献类型：
--
作者：
Bollenbach, Alexander;Schutte, Aletta E.;Tsikas, Dimitrios
蛋白质精氨酸二甲基化 (PADiMe) 是一种主要的翻译后修饰。不对称和对称 PADiMe 产物的蛋白水解分别释放不对称二甲基精氨酸 (ADMA) 和对称二甲基精氨酸 (SDMA)，这两种内源性致动脉粥样硬化物质。 SDMA、ADMA 及其主要代谢物二甲胺 (DMA) 由肾脏消除。 DMA+ADMA、SDMA 和 DMA+ADMA+SDMA 的尿液浓度分别是全身不对称和对称 PADiMe 的有用测量值。尿 (DMA+ADMA)/SDMA 是不对称与对称 PADiMe 平衡的指标。在两项双种族研究 ASOS（39 名黑人男孩，41 名白人男孩）和 Africa-PREDICT（292 名黑人年轻男性，281 名白人年轻男性）研究中，我们调查了种族是否是 PADiMe 的主要决定因素，以及 PADiMe 是否与血压、种族依赖性生长和炎症因子（包括 HDL）相关。通过气相色谱-质谱法测量点尿样品中的 DMA、ADMA 和 SDMA，并根据肌酐排泄量对它们的排泄量进行校正。在黑人男孩中，肌酐校正的 DMA、DMA+ADMA 和 DMA+ADMA+SDMA 浓度分别比白人男孩低 11.7%、9.5% 和 7.6%（所有 p < 0.05），与白人男孩相比，黑人男孩分别低 3.4%、2.0% 和 1.8%（所有 p < 0.05）。 (DMA+ADMA)/SDMA 在黑人男孩和黑人男性之间没有差异，但在白人男孩中高于白人男性。 ADMA 在黑人男孩和白人男孩之间，或者黑人和白人男性之间没有差异。与白人男孩（低 8%）和白人男孩（低 3.1%）相比，黑人男孩的肌酐校正 SDMA 排泄量较低。在这两项研究中，PADiMe 指数均与血压无关。仅在黑人中，IGF 结合蛋白 3 与所有 PADiMe 指数呈负相关。我们的研究表明，白人男孩的不对称蛋白质精氨酸二甲基化程度高于黑人男孩，并且这种差异在成年后消失。与白人受试者相比，黑人受试者的 ADMA 代谢和 SDMA 排泄较低，表明儿童时期 ADMA 和 SDMA 的肝脏和肾脏消除存在种族依赖性。我们的研究结果可能具有动脉粥样硬化以外的临床意义，例如生长和炎症，迄今为止尚未得到充分解决。
Proteinic arginine dimethylation (PADiMe) is a major post-translational modification. Proteolysis of asymmetric and symmetric PADiMe products releases asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), respectively, two endogenous atherogenic substances. SDMA, ADMA, and its major metabolite dimethylamine (DMA) are eliminated by the kidney. The urinary concentrations of DMA+ADMA, SDMA, and DMA+ADMA+SDMA are useful measures of the whole-body asymmetric and symmetric PADiMe, respectively. Urinary (DMA+ADMA)/SDMA is an index of the asymmetric to symmetric PADiMe balance. In two bi-ethnic studies, the ASOS (39 black boys, 41 white boys) and the African-PREDICT (292 black young men, 281 white young men) studies, we investigated whether ethnicity is a major determinant of PADiMe, and whether PADiMe is associated with blood pressure and ethnicity-dependent growth and inflammatory factors, including HDL. DMA, ADMA, and SDMA were measured in spot urine samples by gas chromatography-mass spectrometry, and their excretion was corrected for creatinine excretion. In black boys, creatinine-corrected DMA, DMA+ADMA, and DMA+ADMA+SDMA concentrations were lower by 11.7%, 9.5%, and 7.6% (all p < 0.05), respectively, compared to the white boys, and 3.4%, 2.0%, and 1.8% lower (all p < 0.05), respectively, in black compared to white men. (DMA+ADMA)/SDMA did not differ between black boys and black men, but was higher in white boys compared to white men. ADMA did not differ between black and white boys, or between black and white men. Creatinine-corrected SDMA excretion was lower in black boys compared to white boys (by 8%) and to white men (by 3.1%). None of the PADiMe indices were associated with blood pressure in either study. IGF-binding protein 3 correlated inversely with all PADiMe indices in the black men only. Our study showed that asymmetric proteinic arginine dimethylation is higher in white boys than in black boys, and that this difference disappears in adulthood. ADMA metabolism and SDMA excretion were lower in the black subjects compared to the white subjects, suggesting ethnicity-dependent hepatic and renal elimination of ADMA and SDMA in the childhood. The results of our study may have clinical relevance beyond atherosclerosis, such as in growth and inflammation, which have not been sufficiently addressed thus far.