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2647例芬兰危重症患者中常见的炎症相关候选基因变异与急性肾损伤

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients.

作者信息

Vilander Laura M, Vaara Suvi T, Kaunisto Mari A, Pettilä Ville, Study Group The Finnaki

机构信息

Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine,University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland.

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki,000014 Helsinki, Finland.

出版信息

J Clin Med. 2019 Mar 11;8(3):342. doi: 10.3390/jcm8030342.

Abstract

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, = 625) to controls (Stage 0, = 1582). For genotyping we used iPLEX Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in and rs1800896 in and AKI, we found no association (odds ratios 1.06 (95% CI 0.89⁻1.28, = 0.51) and 0.92 (95% CI 0.80⁻1.05, = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.

摘要

急性肾损伤(AKI)是一种在危重症患者中发病率较高的综合征。由于临床变量和目前使用的生物标志物未能预测个体对AKI的易感性,因此对该性状的候选基因变异进行了研究。关于AKI遗传易感性的研究大多样本量不足且质量中等。我们报告了对一组芬兰危重症患者中27种基因变异的关联研究,重点是对与炎症、细胞存活或循环相关基因变异所检测到的关联进行重复验证。在这项前瞻性观察性芬兰急性肾损伤(FINNAKI)研究中,对2647例无慢性肾病的患者进行了基因分型。我们根据改善全球肾脏病预后组织(KDIGO)标准定义AKI。我们将严重AKI(2期和3期,n = 625)与对照组(0期,n = 1582)进行比较。基因分型采用iPLEX检测法(Agena Bioscience公司)。我们使用PLINK软件进行关联分析,在逻辑回归中采用加性遗传模型。尽管有大量关于白细胞介素6基因多态性rs1800629和肿瘤坏死因子α基因多态性rs1800896与AKI之间关联的研究,尽管这些研究结果相互矛盾,但我们未发现关联(优势比分别为1.06(95%可信区间0.89⁻1.28,P = 0.51)和0.92(95%可信区间0.80⁻1.05,P = 0.20))。对混杂因素进行校正后结果未改变。总之,我们无法在一组危重症患者中证实先前研究报告的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cb8/6463106/5ffe0e4d5449/jcm-08-00342-g001.jpg

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