Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota

IF 2.9 3区医学 Q2 GENETICS & HEREDITY Pharmacogenomics Journal Pub Date : 2022-01-31 DOI:10.1038/s41397-022-00265-9

Guilherme S. Lopes, Jaime L. Lopes, Suzette J. Bielinski, Sebastian M. Armasu, Ye Zhu, Dana C. Cavanaugh, Ann M. Moyer, Debra J. Jacobson, Liwei Wang, Ruoxiang Jiang, Jennifer L. St. Sauver, Nicholas B. Larson

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引用次数: 4

Abstract

The study of sex-specific genetic associations with opioid response may improve the understanding of inter-individual variability in pain treatments. We investigated sex-specific associations between genetic variation and opioid response. We identified participants in the RIGHT Study prescribed codeine, tramadol, hydrocodone, and oxycodone between 01/01/2005 and 12/31/2017. Prescriptions were collapsed into codeine/tramadol and hydrocodone/oxycodone. Outcomes included poor pain control and adverse reactions within six weeks after prescription date. We performed gene-level and single-variant association analyses stratified by sex. We included 7169 non-Hispanic white participants and a total of 1940 common and low-frequency variants (MAF > 0.01). Common variants in MACROD2 (rs76026520), CYP1B1 (rs1056837, rs1056836), and CYP2D6 (rs35742686) were associated with outcomes. At the gene level, FAAH, SCN1A, and TYMS had associations for men and women, and NAT2, CYP3A4, CYP1A2, and SLC22A2 had associations for men only. Our findings highlight the importance of considering sex in association studies on opioid response.

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明尼苏达州东南部非西班牙裔白人队列中阿片类镇痛药反应的性别特异性遗传关联鉴定

对阿片类药物反应的性别特异性遗传关联进行研究，可加深对疼痛治疗中个体间差异的理解。我们研究了基因变异与阿片类药物反应之间的性别特异性关联。我们确定了 RIGHT 研究的参与者在 2005 年 1 月 1 日至 2017 年 12 月 31 日期间开具的可待因、曲马多、氢可酮和羟考酮处方。处方分为可待因/曲马多和氢可酮/羟考酮。结果包括疼痛控制不佳和处方日期后六周内的不良反应。我们按性别进行了基因水平和单变体关联分析。我们纳入了 7169 名非西班牙裔白人参与者和共计 1940 个常见和低频变异（MAF > 0.01）。MACROD2（rs76026520）、CYP1B1（rs1056837、rs1056836）和 CYP2D6（rs35742686）中的常见变异与结果相关。在基因水平上，FAAH、SCN1A 和 TYMS 对男性和女性都有关联，而 NAT2、CYP3A4、CYP1A2 和 SLC22A2 仅对男性有关联。我们的研究结果凸显了在阿片类药物反应关联研究中考虑性别因素的重要性。

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来源期刊

Pharmacogenomics Journal 医学-药学

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The Pharmacogenomics Journal is a print and electronic journal, which is dedicated to the rapid publication of original research on pharmacogenomics and its clinical applications. Key areas of coverage include: Personalized medicine Effects of genetic variability on drug toxicity and efficacy Identification and functional characterization of polymorphisms relevant to drug action Pharmacodynamic and pharmacokinetic variations and drug efficacy Integration of new developments in the genome project and proteomics into clinical medicine, pharmacology, and therapeutics Clinical applications of genomic science Identification of novel genomic targets for drug development Potential benefits of pharmacogenomics.