Division of Medical Toxicology, Department of Emergency Medicine, Mount Sinai School of Medicine, Elmhurst Hospital Center, New York, NY 10029, USA.
J Med Toxicol. 2013 Jun;9(2):148-54. doi: 10.1007/s13181-012-0286-3.
Genetic variations in the human mu-opioid receptor gene (OPRM1) mediate individual differences in response to pain and opiate addiction. We studied whether the common A118G (rs1799971) mu-opioid receptor single nucleotide polymorphism (SNP) was associated with overdose severity in humans. In addition, we examined an SNP responsible for alternative splicing of OPRM1 (rs2075572). We assessed allele frequencies of the above SNPs and associations with clinical severity in patients presenting to the emergency department (ED) with acute drug overdose. This work was designed as an observational cohort study over a 12-month period at an urban teaching hospital. Participants consisted of consecutive adult ED patients with suspected acute drug overdose for whom discarded blood samples were available for analysis. Specimens were linked with clinical variables (demographics, urine toxicology screens, clinical outcomes) then deidentified prior to genetic SNP analysis. Blinded genotyping was performed after standard DNA purification and whole genome amplification. In-hospital severe outcomes were defined as either respiratory arrest (RA; defined by mechanical ventilation) or cardiac arrest (CA; defined by loss of pulse). We analyzed 179 patients (61% male, median age 32) who overall suffered 15 RAs and four CAs, of whom three died. The 118G allele conferred 5.3-fold increased odds of CA/RA (p<0.05), while the rs2075572 variant allele was not associated with CA/RA. The 118G variant allele in the OPRM1 gene is associated with worse clinical severity in patients with acute drug overdose. These findings mark the first time that the 118G variant allele is linked with clinical drug overdose vulnerability.
人类阿片μ受体基因（OPRM1）中的遗传变异可介导个体对疼痛和阿片类药物成瘾的反应差异。我们研究了常见的 A118G（rs1799971）阿片μ受体单核苷酸多态性（SNP）是否与人类过量严重程度相关。此外，我们还研究了导致 OPRM1 剪接变异的 SNP（rs2075572）。我们评估了上述 SNP 的等位基因频率，并在因急性药物过量就诊于急诊科的患者中评估了它们与临床严重程度的相关性。这项工作是在一家城市教学医院进行的为期 12 个月的观察性队列研究。参与者包括连续就诊于急诊科、疑似急性药物过量的成年患者，他们的废弃血液样本可用于分析。在进行基因 SNP 分析之前，将标本与临床变量（人口统计学、尿液毒物筛查、临床结局）相关联，并进行匿名处理。在进行标准 DNA 纯化和全基因组扩增后，进行盲法基因分型。住院期间严重结局定义为呼吸暂停（RA；定义为机械通气）或心脏骤停（CA；定义为脉搏丧失）。我们分析了 179 名患者（61%为男性，中位年龄 32 岁），他们总共发生了 15 例 RA 和 4 例 CA，其中 3 例死亡。118G 等位基因使 CA/RA 的发生几率增加了 5.3 倍（p<0.05），而 rs2075572 变异等位基因与 CA/RA 无关。OPRM1 基因中的 118G 变异等位基因与急性药物过量患者的临床严重程度增加有关。这些发现首次表明，118G 变异等位基因与临床药物过量易感性有关。
