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Candidate gene analyses for acute pain and morphine analgesia after pediatric day surgery: African American versus European Caucasian ancestry and dose prediction limits.
The Pharmacogenomics Journal ( IF 2.8 ) Pub Date : 2019-02-14 , DOI: 10.1038/s41397-019-0074-4
Jin Li 1, 2 , Zhi Wei 3 , Jie Zhang 3 , Hakon Hakonarson 2, 4 , Scott D Cook-Sather 4, 5
Affiliation  

Acute pain and opioid analgesia demonstrate inter-individual variability and polygenic influence. In 241 children of African American and 277 of European Caucasian ancestry, we sought to replicate select candidate gene associations with morphine dose and postoperative pain and then to estimate dose prediction limits. Twenty-seven single-nucleotide polymorphisms (SNPs) from nine genes (ABCB1, ARRB2, COMT, DRD2, KCNJ6, MC1R, OPRD1, OPRM1, and UGT2B7) met selection criteria and were analyzed along with TAOK3. Few associations replicated: morphine dose (mcg/kg) in African American children and ABCB1 rs1045642 (A allele, β = -9.30, 95% CI: -17.25 to -1.35, p = 0.02) and OPRM1 rs1799971 (G allele, β = 23.19, 95% CI: 3.27-43.11, p = 0.02); KCNJ6 rs2211843 and high pain in African American subjects (T allele, OR 2.08, 95% CI: 1.17-3.71, p = 0.01) and in congruent European Caucasian pain phenotypes; and COMT rs740603 for high pain in European Caucasian subjects (A allele, OR: 0.69, 95% CI: 0.48-0.99, p = 0.046). With age, body mass index, and physical status as covariates, simple top SNP candidate gene models could explain theoretical maximums of 24.2% (European Caucasian) and 14.6% (African American) of morphine dose variances.

中文翻译:

儿科日间手术后急性疼痛和吗啡镇痛的候选基因分析:非洲裔美国人与欧洲白种人血统和剂量预测限制。

急性疼痛和阿片类镇痛表现出个体差异和多基因影响。在 241 名非裔美国人和 277 名欧洲白种人血统的儿童中,我们试图复制选择的候选基因与吗啡剂量和术后疼痛的关联,然后估计剂量预测限值。来自九个基因(ABCB1、ARRB2、COMT、DRD2、KCNJ6、MC1R、OPRD1、OPRM1 和 UGT2B7)的 27 个单核苷酸多态性 (SNP) 符合选择标准,并与 TAOK3 一起分析。很少有关联重复:非裔美国儿童的吗啡剂量 (mcg/kg) 和 ABCB1 rs1045642(A 等位基因,β = -9.30,95% CI:-17.25 至 -1.35,p = 0.02)和 OPRM1 rs1799971(G 等位基因,β = 23.19, 95% CI: 3.27-43.11, p = 0.02); KCNJ6 rs2211843 和非裔美国人受试者的高度疼痛(T 等位基因,OR 2.08,95% CI:1.17-3.71,p = 0。01) 和一致的欧洲高加索疼痛表型;和 COMT rs740603 用于欧洲高加索受试者的高痛(A 等位基因,OR:0.69,95% CI:0.48-0.99,p = 0.046)。以年龄、体重指数和身体状况作为协变量,简单的顶级 SNP 候选基因模型可以解释 24.2%(欧洲高加索人)和 14.6%(非洲裔美国人)吗啡剂量差异的理论最大值。
更新日期:2019-11-18
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