Septic shock is correlated with asymmetrical dimethyl arginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study
Septic shock is correlated with asymmetrical dimethyl arginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study
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DOI：
10.1186/cc5053
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发表时间：
2006-01-01
期刊：
影响因子：
15.1
通讯作者：
Ryan, Thomas
中科院分区：
文献类型：
--
作者：
O'Dwyer, Michael J.;Dempsey, Felicity;Ryan, Thomas
前言不对称二甲基精氨酸（ADMA）是一种内源性非选择性一氧化氮合酶抑制剂，可能会影响器官衰竭的严重程度和继发于感染性损伤的休克的发生。水平可通过编码二甲基精氨酸二甲氨基水解酶II（DDAH II）的调节基因中的启动子多态性遗传决定，DDAH II通过将ADMA代谢为瓜氨酸发挥作用。本研究的目的是研究ADMA水平和严重脓毒症的器官衰竭和休克的严重程度之间的关联，并评估DDAH II的启动子多态性对ADMA levels.Methods的影响前瞻性观察研究设计，47重症监护病房（ICU）严重脓毒症患者和10名健康对照。在进入ICU时和7天后测定血清ADMA和IL-6。在DDAH II基因的位置-449多态性的等位基因变异进行了评估，在每个病人。结果在第1天，ICU组比对照组检测到更多的ADMA（p = 0.005）。随后在ICU的第一周内水平升高（p = 0.001）。ADMA水平与第一天的血管加压药需求相关（p = 0.001）。ADMA水平和序贯器官衰竭评估评分在第1天（p = 0.0001）和第7天（p = 0.002）直接相关。酸血症和乳酸血症的程度与两个时间点的ADMA水平直接相关（p < 0.01）。在第7天，IL-6与ADMA水平直接相关（p = 0.006）。DDAH Ⅱ基因-449位点G变异等位基因与ADMA浓度升高相关（p < 0.05）。结论严重脓毒症患者ADMA浓度升高与器官功能衰竭、炎症反应及早期休克有关。ADMA浓度可能受到DDAH II基因多态性的影响。
Introduction Asymmetrical dimethyl arginine ( ADMA) is an endogenous non-selective inhibitor of nitric oxide synthase that may influence the severity of organ failure and the occurrence of shock secondary to an infectious insult. Levels may be genetically determined by a promoter polymorphism in a regulatory gene encoding dimethylarginine dimethylaminohydrolase II (DDAH II), which functions by metabolising ADMA to citrulline. The aim of this study was to examine the association between ADMA levels and the severity of organ failure and shock in severe sepsis and also to assess the influence of a promoter polymorphism in DDAH II on ADMA levels.Methods A prospective observational study was designed, and 47 intensive care unit (ICU) patients with severe sepsis and 10 healthy controls were enrolled. Serum ADMA and IL-6 were assayed on admission to the ICU and seven days later. Allelic variation for a polymorphism at position - 449 in the DDAH II gene was assessed in each patient. Clinical and demographic details were also collected.Results On day 1 more ADMA was detectable in the ICU group than in the control group ( p = 0.005). Levels subsequently increased during the first week in ICU ( p = 0.001). ADMA levels were associated with vasopressor requirements on day one ( p = 0.001). ADMA levels and Sequential Organ Failure Assessment scores were directly associated on day one ( p = 0.0001) and day seven ( p = 0.002). The degree of acidaemia and lactaemia was directly correlated with ADMA levels at both time points ( p < 0.01). On day seven, IL-6 was directly correlated with ADMA levels ( p = 0.006). The variant allele with G at position - 449 in the DDAH II gene was associated with increased ADMA concentrations at both time points ( p < 0.05).Conclusion Severity of organ failure, inflammation and presence of early shock in severe sepsis are associated with increased ADMA levels. ADMA concentrations may be influenced by a polymorphism in the DDAH II gene.