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NADPH氧化酶p22phox的C242T多态性与冠状动脉疾病心血管事件的复发

C242T polymorphism of NADPH oxidase p22phox and recurrence of cardiovascular events in coronary artery disease.

作者信息

Arca Marcello, Conti Beatrice, Montali Anna, Pignatelli Pasquale, Campagna Filomena, Barillà Francesco, Tanzilli Gaetano, Verna Roberto, Vestri Annarita, Gaudio Carlo, Violi Francesco

机构信息

Department of Clinical and Medical Therapy, Unit of Medical Therapy, La Sapienza University, Rome, Italy.

出版信息

Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):752-7. doi: 10.1161/ATVBAHA.107.154823. Epub 2008 Jan 31.

DOI:10.1161/ATVBAHA.107.154823
PMID:18239158
Abstract

OBJECTIVE

The common C242T polymorphism in the gene for the p22phox subunit of NADPH oxidase has been reported to be negatively associated with oxidative stress, but whether it confers prognostic information is not yet clear.

METHODS AND RESULTS

The incidence of major adverse cardiovascular events (MACE) were determined in 237 patients with coronary stenosis during a median follow-up of 7.8 years. The p22phox genotypes were evaluated in 213 patients (89.9%) by polymerase chain reaction and RsaI. digestion. Plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, were also measured. In the univariate analysis, patients with CT/TT genotypes showed reduced recurrence of cardiovascular deaths, nonfatal MI, and revascularization procedures compared with homozygous carriers of the C allele. After controlling for confounders, a significantly lower risk of new revascularization procedures (HR=0.31, 95% CI 0.12 to 0.70; P=0.014) remained associated with the T allele. The Kaplan-Meier analysis showed a longer survival free from fatal and nonfatal MI in carriers of T allele (P<0.001). The presence of the 242T allele was associated with significantly reduced plasma concentrations of 8-OHdG.

CONCLUSIONS

The 242T allele was a predictor of lower risk of recurrence of cardiovascular events in high-risk patients and was associated with reduced systemic oxidative stress.

摘要

目的

据报道,烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶p22phox亚基基因中常见的C242T多态性与氧化应激呈负相关,但它是否能提供预后信息尚不清楚。

方法与结果

在237例冠状动脉狭窄患者中确定主要不良心血管事件(MACE)的发生率,中位随访时间为7.8年。通过聚合酶链反应和RsaI酶切对213例患者(89.9%)的p22phox基因型进行评估。还测量了氧化应激标志物8-羟基-2'-脱氧鸟苷(8-OHdG)的血浆水平。在单因素分析中,与C等位基因纯合携带者相比,CT/TT基因型患者的心血管死亡、非致命性心肌梗死和血运重建手术的复发率降低。在控制混杂因素后,T等位基因仍与新的血运重建手术风险显著降低相关(HR=0.31,95%CI 0.12至0.70;P=0.014)。Kaplan-Meier分析显示,T等位基因携带者无致命性和非致命性心肌梗死的生存期更长(P<0.001)。242T等位基因的存在与8-OHdG血浆浓度显著降低相关。

结论

242T等位基因是高危患者心血管事件复发风险较低的预测指标,且与全身氧化应激降低相关。

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