Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
PLoS One. 2019 May 23;14(5):e0217291. doi: 10.1371/journal.pone.0217291. eCollection 2019.
Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk.
急性肾损伤（AKI）是一种经常影响危重病患者的综合征。最近，有报道称，HMOX1 基因中的二核苷酸重复增加与心脏手术后 AKI 的发生有关。我们旨在芬兰危重病脓毒症患者队列中检验这一发现的可重复性。这项多中心研究是国家 FINNAKI 研究的一部分。我们对 300 名严重 AKI（KDIGO 2 或 3）患者和 353 名无 AKI（KDIGO 0）患者进行了 HMOX1 基因启动子区鸟嘌呤-胸腺嘧啶（GTn）重复的基因分型。等位基因的调用是基于重复的数量，截断值在 S-L（短到长）分类中为 27 个重复，在 S-M-L2（短到中到非常长）分类中为 27 和 34 个重复。入院时测量血红素加氧酶-1（HO-1）酶的血浆浓度。我们患者的等位基因分布与之前发表的结果相似，在 23 和 30 个重复处出现高峰。S 等位基因增加 AKI 风险。在加性遗传模型中，每个 S 等位基因的调整 OR 为 1.30（95%CI 1.01-1.66；p=0.041）。重复数大于 34 的等位基因与 HO-1 浓度显著降低相关（p<0.001）。在脓毒症患者中，我们报告了 HMOX1 中的短重复与 AKI 风险之间的关联。
