Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland.
Biostatistics Consulting, Department of Public Health, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland.
Acta Anaesthesiol Scand. 2023 Sep;67(8):1018-1027. doi: 10.1111/aas.14261. Epub 2023 May 8.
The incidence of post-operative nausea and vomiting (PONV) remains at about 30% despite all therapeutic efforts to reduce it. The clinical risk factors guiding the prophylactic treatment are well established, but genetic factors associated with PONV remain poorly known. The aim of this study was to explore clinical and genetic factors impacting PONV by performing a genome-wide association study (GWAS) together with relevant clinical factors as covariates, and systematically attempt to replicate previously reported PONV associations. Relevant clinical factors are explored with logistic regression model.
This was an observational case control study in Helsinki University Hospital between 1 August 2006 and 31 December 2010. One thousand consenting women with elevated risk for PONV, undergoing breast cancer surgery with standardised propofol anaesthesia and antiemetics. After exclusions for clinical reasons and failed genotyping, 815 patients were included with 187 PONV cases and 628 controls. Emergence of PONV up to 7th post-operative day was recorded. PONV at 2-24 h after surgery was selected to be the primary outcome. The GWAS explored associations between PONV and 653 034 genetic variants. Replication attempts included 31 variants in 16 genes.
The overall incidence of PONV up to 7th post-operative day was 35%, where 3% had PONV at 0-2 h and 23% at 2-24 h after surgery. Age, American Society of Anaesthesiologists status, the amount of oxycodone used in the post-anaesthesia care unit, smoking status, previous PONV, and history of motion sickness were statistically significant predictive factors in the logistic model. The receiver operating characteristic-area under the curve of 0.75 (95% CI 0.71-0.79) was calculated for the model. The GWAS identified six variants with suggestive association to PONV (p < 1 × 10 ). Of the previously reported variants, association with the DRD2 variant rs18004972 (TaqIA) was replicated (p = .028).
Our GWAS approach did not identify any high-impact PONV susceptibility variants. The results provide some support for a role of dopamine D receptors in PONV.
尽管采取了各种治疗措施来降低术后恶心和呕吐（PONV）的发生率，但术后恶心和呕吐的发生率仍约为 30%。指导预防性治疗的临床危险因素已经确定，但与 PONV 相关的遗传因素仍知之甚少。本研究旨在通过全基因组关联研究（GWAS）结合相关临床因素作为协变量来探讨影响 PONV 的临床和遗传因素，并系统地尝试复制先前报道的 PONV 相关性。使用逻辑回归模型探讨相关临床因素。
这是 2006 年 8 月 1 日至 2010 年 12 月 31 日在赫尔辛基大学医院进行的一项观察性病例对照研究。选择 1000 名患有 PONV 风险升高的患者，接受标准的异丙酚麻醉和止吐药治疗。排除因临床原因和基因分型失败后，815 名患者纳入研究，其中 187 例发生 PONV，628 例为对照组。记录术后第 7 天的 PONV 发作情况。选择术后 2-24 小时的 PONV 作为主要结局。GWAS 研究了 PONV 与 653034 个遗传变异之间的相关性。在 16 个基因中，复制尝试包括 31 个变体。
术后第 7 天的 PONV 总发生率为 35%，其中 3%在术后 0-2 小时出现 PONV，23%在术后 2-24 小时出现 PONV。年龄、美国麻醉医师协会状态、麻醉后护理病房使用的羟考酮量、吸烟状态、PONV 病史和晕动病史是逻辑模型中具有统计学意义的预测因素。模型的接收者操作特征曲线下面积为 0.75（95%CI 0.71-0.79）。GWAS 鉴定出 6 个与 PONV 相关的提示性变异（p<1×10）。先前报道的变体与 DRD2 变体 rs18004972（TaqIA）的相关性得到复制（p=0.028）。
我们的 GWAS 方法没有发现任何高影响的 PONV 易感性变异。结果为多巴胺 D 受体在 PONV 中的作用提供了一些支持。
