Abstract：
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 × 10-5 ). 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 D2 receptors in PONV.
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 × 10-5 ). 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 D2 receptors in PONV.
摘要：
背景：术后恶心和呕吐（PONV）的发生率保持在约30％，尽管所有的治疗努力降低它。指导预防性治疗的临床危险因素已经确立，但与PONV相关的遗传因素仍然知之甚少。这项研究的目的是通过进行全基因组关联研究（GWAS）以及相关临床因素作为协变量来探索影响PONV的临床和遗传因素。并系统地尝试复制先前报告的PONV关联。采用logistic回归模型探讨相关临床因素。
方法：这是一项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观察性病例对照研究。一千名同意患PONV风险升高的女性，接受标准化丙泊酚麻醉和止吐药的乳腺癌手术。在因临床原因排除和基因分型失败后，815例患者包括187例PONV病例和628例对照。记录直到术后第7天的PONV出现。选择手术后2-24小时的PONV作为主要结果。GWAS研究了PONV和653034个遗传变异之间的关联。复制尝试包括16个基因中的31个变体。
结果：术后第7天PONV的总发生率为35%，其中3%在手术后0-2小时出现PONV，23%在手术后2-24小时出现PONV。年龄,美国麻醉医师协会的地位，麻醉后护理单元中使用的羟考酮的量，吸烟状况,以前的PONV,在逻辑模型中，运动病史是统计学上有意义的预测因素。计算模型的受试者工作特征-曲线下面积为0.75（95％CI0.71-0.79）。GWAS鉴定出与PONV有暗示性关联的6个变异体(p<1×10-5)。在先前报道的变体中，与DRD2变体rs18004972(TaqIA)的关联被重复(p=.028)。
结论：我们的GWAS方法没有发现任何高影响PONV易感性变异。该结果为多巴胺D2受体在PONV中的作用提供了一些支持。
方法：这是一项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观察性病例对照研究。一千名同意患PONV风险升高的女性，接受标准化丙泊酚麻醉和止吐药的乳腺癌手术。在因临床原因排除和基因分型失败后，815例患者包括187例PONV病例和628例对照。记录直到术后第7天的PONV出现。选择手术后2-24小时的PONV作为主要结果。GWAS研究了PONV和653034个遗传变异之间的关联。复制尝试包括16个基因中的31个变体。
结果：术后第7天PONV的总发生率为35%，其中3%在手术后0-2小时出现PONV，23%在手术后2-24小时出现PONV。年龄,美国麻醉医师协会的地位，麻醉后护理单元中使用的羟考酮的量，吸烟状况,以前的PONV,在逻辑模型中，运动病史是统计学上有意义的预测因素。计算模型的受试者工作特征-曲线下面积为0.75（95％CI0.71-0.79）。GWAS鉴定出与PONV有暗示性关联的6个变异体(p<1×10-5)。在先前报道的变体中，与DRD2变体rs18004972(TaqIA)的关联被重复(p=.028)。
结论：我们的GWAS方法没有发现任何高影响PONV易感性变异。该结果为多巴胺D2受体在PONV中的作用提供了一些支持。
