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氧化应激相关基因与冠状动脉粥样硬化程度的关联

Association of Genes Related to Oxidative Stress with the Extent of Coronary Atherosclerosis.

作者信息

Racis Milena, Stanisławska-Sachadyn Anna, Sobiczewski Wojciech, Wirtwein Marcin, Krzemiński Michał, Krawczyńska Natalia, Limon Janusz, Rynkiewicz Andrzej, Gruchała Marcin

机构信息

First Department of Cardiology, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland.

Department of Biology and Genetics, Medical University of Gdańsk, ul. Dębinki 1, 80-211 Gdańsk, Poland.

出版信息

Life (Basel). 2020 Sep 18;10(9):210. doi: 10.3390/life10090210.

Abstract

Oxidative stress is believed to play a critical role in atherosclerosis initiation and progression. In line with this, in a group of 1099 subjects, we determined eight single nucleotide polymorphisms (SNPs) related to oxidative stress ( c.575A>G, c.-463G>A, c.47T>C, c.-590C>T, c.894G>T, c.-786T>C, c.214C>T, and c.-932A>G) and assessed the extent of atherosclerosis in coronary arteries based on Gensini score. An increased risk of having a Gensini score in the higher half of the distribution was observed for the c.575G allele (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.004-1.617, = 0.046). Next, the genetic risk score (GRS) for the additive effect of the total number of pro-oxidative alleles was assessed. We noted an increase in the risk of having a Gensini score above the median with the maximum number of risk alleles (OR = 2.47, 95% CI: 1.19-5.23, = 0.014). A univariate Spearman's test revealed significant correlation between the total number of pro-oxidant alleles (GRS) and the Gensini score (ρ = 0.068, = 0.03). In conclusion, the c.575A>G variant and the high number of risk alleles (GRS) were independent risk factors for a high Gensini score. We suggest, however, that GRS might occur as a more valuable component in adding a predictive value to the genetic background of atherosclerosis.

摘要

氧化应激被认为在动脉粥样硬化的发生和发展中起关键作用。与此相符的是,在一组1099名受试者中,我们测定了与氧化应激相关的8个单核苷酸多态性(SNP)(c.575A>G、c.-463G>A、c.47T>C、c.-590C>T、c.894G>T、c.-786T>C、c.214C>T和c.-932A>G),并根据Gensini评分评估冠状动脉粥样硬化的程度。对于c.575G等位基因,观察到Gensini评分处于分布上半部分的风险增加(优势比(OR)=1.27,95%置信区间(CI):1.004 - 1.617,P = 0.046)。接下来,评估了促氧化等位基因总数的加性效应的遗传风险评分(GRS)。我们注意到,具有最大风险等位基因数时,Gensini评分高于中位数的风险增加(OR = 2.47,95% CI:1.19 - 5.23,P = 0.014)。单变量Spearman检验显示促氧化等位基因总数(GRS)与Gensini评分之间存在显著相关性(ρ = 0.068,P = 0.03)。总之,c.575A>G变异和高风险等位基因数(GRS)是高Gensini评分的独立危险因素。然而,我们认为GRS可能是一个更有价值的成分,可为动脉粥样硬化的遗传背景增加预测价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a29/7554836/b397cdf4a929/life-10-00210-g001.jpg

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