多巴胺D2受体基因SNP rs1800497与术后恶心和呕吐的关联:一项前瞻性队列研究

Maike Stegen, Hagen S Bachmann, Grazina Belani, Ahmed Mohamed, Björn Breuing, Thorsten Brenner, Stefanie Klenke
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引用次数: 0

摘要

背景:术后恶心呕吐(PONV)是麻醉中最常见的并发症。几项研究表明遗传性状对PONV倾向的贡献。胆碱能受体毒碱碱3基因CHRM3 (rs2165870)和钾电压门控通道亚家族B成员2 KCNB2 (rs349358)的单核苷酸多态性(snp)被认为是PONV发生的独立危险因素。此外,其他SNP可能与PONV风险增加有关,例如多巴胺D2受体(DRD2) SNP (rs1800497)。目的:我们研究的主要目的是建立一种新的PONV预测评分,该评分包括CHRM3和KCNB2基因的snp遗传信息,这两个基因已经与PONV相关。我们研究的第二个目的是调查另外五个snp与PONV的关系。设计:前瞻性队列研究。环境:德国单中心学习。结果:由于KCNB2 SNP和CHRM3 SNP与PONV的关联有限,我们无法建立包含遗传信息的新的PONV预测评分。有趣的是,多巴胺D2受体基因DRD2 rs1800497的GA和AA基因型与术后24 h PONV相关,GA/AA基因型与GG基因型的相对危险度(RR)为1.5[95%置信区间(CI) 1.06 ~ 2.01, P = 0.02]。在多变量logistic回归分析中,这种关联与Apfel评分无关(RR 1.4, 95% CI 1.03 ~ 1.90, P = 0.03)。结论:由于CHRM3和KCNB2 snp的关联有限,构建包含遗传信息的新的PONV预测评分是不可能的。然而,DRD2 GA和AA基因型(rs1800497)与PONV相关,该SNP可能是未来进一步验证研究的候选者,旨在建立分子衍生的PONV预测模型。试验注册:德国临床研究注册- DRKS00021051。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Association of the dopamine D2 receptor gene SNP rs1800497 with postoperative nausea and vomiting: A prospective cohort study.

Background: Postoperative nausea and vomiting (PONV) are the most frequent complications in the context of anaesthesia. Several studies suggest a contribution of genetic traits to PONV disposition. Single nucleotide polymorphisms (SNPs) located in the cholinergic receptor muscarinic 3 gene CHRM3 (rs2165870) and the potassium voltage-gated channel subfamily B member 2 KCNB2 (rs349358) have been described as independent risk factors for the occurrence of PONV. In addition, further SNPs might be associated with an increased PONV risk, for example a dopamine D2 receptor (DRD2) SNP (rs1800497).

Objective: The primary aim of our study was the development of a new PONV prediction score which includes genetic information of SNPs in the genes CHRM3 and KCNB2, which have been already associated with PONV. The secondary aim of our study was to investigate the association of five additional SNPs with PONV.

Design: Prospective cohort study.

Setting: Single centre study in Germany.

Results: We could not establish a new PONV prediction score that includes genetic information, due to limited association of the KCNB2 SNP and CHRM3 SNP with PONV. Interestingly, the GA and AA genotypes of the DRD2 rs1800497 in the dopamine D2 receptor gene were associated with PONV 24 h postoperatively, with a relative risk (RR) of GA/AA genotype vs. GG genotype of 1.5 [95% confidence interval (CI) 1.06 to 2.01, P = 0.02]. This association was independent from the Apfel score in a multivariate logistic regression analysis (RR 1.4, 95% CI 1.03 to 1.90, P = 0.03).

Conclusion: The construction of a new PONV prediction score including genetic information was not possible due to limited association of the CHRM3 and KCNB2 SNPs. However, the DRD2 GA and AA genotypes (rs1800497) were associated with PONV and this SNP might be a future candidate for further validation studies aiming for molecular-derived PONV prediction models.

Trial registration: German Clinical Study Register - DRKS00021051.

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