Association of human NAD(P)H:quinone oxidoreductase 1 (NQO1) polymorphism with development of acute lung injury.
Association of human NAD(P)H:quinone oxidoreductase 1 (NQO1) polymorphism with development of acute lung injury.
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DOI：
10.1111/j.1582-4934.2008.00581.x
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发表时间：
2009-08
影响因子：
5.3
通讯作者：
Kleeberger SR
中科院分区：
文献类型：
--
作者：
Reddy AJ;Christie JD;Aplenc R;Fuchs B;Lanken PN;Kleeberger SR
急性肺损伤(ALI)是一种发病率和死亡率都很高的综合征，但其遗传易感性尚不清楚。在本研究中，我们研究了II相抗氧化剂基因NQO1(NAD(P)H：Quinone oxoreductase1)的功能启动子单核苷酸多态性(SNPs)，以评估其在ALI易感性中的作用。本研究选取了NQO1启动子中三个未知的SNPs进行研究。荧光素酶检测使用每个启动子的多态结构来评估功能。在重大创伤患者(N=264)的前瞻性队列中，对功能性SNP进行了基因分型，并评估了其与ALI发生的相关性。在高氧和其他氧化应激源作用下，NQO1基因-1221位的A/C SNP在体外转录水平降低。即使在调整了APACHE III评分和创伤机制后，携带-1221C等位基因杂合子的患者发生严重创伤后ALI的风险也明显低于携带野生型等位基因的患者[OR，0.46(95%CI，0.23，0.90)；p=0.024]。这项研究表明，NQO1基因-1221位的AC基因型导致转录减少，并与严重创伤后较低的ALI发生率有关。这些新的发现可能对氧化应激引起的疾病有重要的意义。
Acute lung injury (ALI) is a syndrome with significant morbidity and mortality, but its genetic susceptibility is not clearly understood. In the present study, we characterized functional promoter single nucleotide polymorphisms (SNPs) in the phase II antioxidant gene NQO1 (NAD(P)H:quinone oxidoreductase1) to evaluate its role in susceptibility to ALI. Three previously uncharacterized SNPs in the NQO1 promoter were selected for investigation. Luciferase assays were performed using constructs of each promoter polymorphism to evaluate function. Functional SNPs were genotyped in prospective cohort of major trauma patients (N = 264) and assessed for association with development of ALI. The A/C SNP at -1221decreased in vitro transcription of NQO1 at baseline and after exposure to hyperoxia and other oxidant stressors. Patients heterozygous for the -1221 C allele were at significantly lesser risk of ALI after major trauma compared with patients with wild type alleles, even after adjustment for APACHE III score, and mechanism of trauma [OR, 0.46 (95% CI, 0.23, 0.90); p = 0.024]. This study demonstrated that the AC genotype at position -1221 in the NQO1 gene caused decreased transcription and was associated with a lower incidence of ALI following major trauma. These novel findings may have important implications in diseases with oxidant stress etiologies.
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影响因子：
8.8
作者：
Goss, CH;Brower, RG;Rubenfeld, GD
通讯作者：
Rubenfeld, GD
DOI：
10.1073/pnas.0500815102
发表时间：
2005-03-22
影响因子：
11.1
作者：
Dinkova-Kostova, AT;Liby, KT;Talalay, P
通讯作者：
Talalay, P
DOI：
10.1165/rcmb.2005-0404oc
发表时间：
2006-04-01
影响因子：
6.4
作者：
Gao, L;Grant, A;Garcia, JGN
通讯作者：
Garcia, JGN
影响因子：
14.9
作者：
Heinemeyer, T;Wingender, E;Kolchanov, NA
通讯作者：
Kolchanov, NA
影响因子：
3.5
作者：
Wang, Xuting;Tomso, Daniel J.;Bell, Douglas A.
通讯作者：
Bell, Douglas A.