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
{"title":"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","authors":"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","doi":"10.1038/s41397-022-00265-9","DOIUrl":null,"url":null,"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.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975736/pdf/","citationCount":"4","resultStr":"{\"title\":\"Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota\",\"authors\":\"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\",\"doi\":\"10.1038/s41397-022-00265-9\",\"DOIUrl\":null,\"url\":null,\"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.\",\"PeriodicalId\":54624,\"journal\":{\"name\":\"Pharmacogenomics Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2022-01-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975736/pdf/\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacogenomics Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41397-022-00265-9\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacogenomics Journal","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41397-022-00265-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Identification of sex-specific genetic associations in response to opioid analgesics in a White, non-Hispanic cohort from Southeast Minnesota
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.
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.