Analysis of genetic and clinical factors associated with buprenorphine response.
Analysis of genetic and clinical factors associated with buprenorphine response.
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DOI：
10.1016/j.drugalcdep.2021.109013
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发表时间：
2021-10-01
影响因子：
4.2
通讯作者：
Kranzler, Henry R.
中科院分区：
文献类型：
--
作者：
Crist, Richard C.;Vickers-Smith, Rachel;Kember, Rachel L.;Rentsch, Christopher T.;Xu, Heng;Edelman, E. Jennifer;Hartwell, Emily E.;Kampman, Kyle M.;Kranzler, Henry R.
关键词：
丁丙诺啡，批准用于治疗阿片类药物使用障碍（OUD），是不是同样有效的所有患者。候选基因研究表明，在确定丁丙诺啡治疗反应的遗传调节剂方面取得的成功有限。我们研究了1，616名参加百万退伍军人计划的欧洲血统个体，其中1，609人的ICD-9/10代码与OUD一致，180天的丁丙诺啡治疗暴露和全基因组基因型数据。我们对丁丙诺啡治疗反应进行了全基因组关联研究（GWAS）[定义为首次处方后无阿片类药物阳性尿液药物筛查（UDS）]。我们还在多变量分析中检查了丁丙诺啡治疗反应的相关性。虽然没有变异达到全基因组显著性，但有6个位点具有名义上的显著性（p<1 × 10−5），其中4个位于先前表征的基因附近：rs756770（ADAMTSL 2），rs 11782370（SLC 25 A37），rs7205113（CRISPLD 2）和rs 13169373（LINC 01947）。丁丙诺啡每日最大剂量较高（aOR=0.98; 95%CI：0.97，0.995）、UDS数量较多（aOR=0.97; 95%CI：0.96，0.99）和丙型肝炎（HCV）感染史（aOR=0.71; 95%CI：0.57，0.88）与丁丙诺啡应答几率降低相关。年龄较大（aOR：1.01; 95%CI：1.000，1.02）与丁丙诺啡反应几率增加相关。这项研究的统计能力有限，无法检测与复杂人类表型（如丁丙诺啡治疗反应）相关的遗传变异。需要对多个数据集进行荟萃分析，以确保丁丙诺啡治疗反应的GWAS具有足够的统计把握度。丁丙诺啡治疗反应的最稳健的表型预测因子是静脉内药物使用，其代表是HCV感染。
Buprenorphine, approved for treating opioid use disorder (OUD), is not equally efficacious for all patients. Candidate gene studies have shown limited success in identifying genetic moderators of buprenorphine treatment response. We studied 1,616 European-ancestry individuals enrolled in the Million Veteran Program, of whom 1,609 had an ICD-9/10 code consistent with OUD, a 180-day buprenorphine treatment exposure, and genome-wide genotype data. We conducted a genome-wide association study (GWAS) of buprenorphine treatment response [defined as having no opioid-positive urine drug screens (UDS) following the first prescription]. We also examined correlates of buprenorphine treatment response in multivariable analyses. Although no variants reached genome-wide significance, 6 loci were nominally significant (p<1 × 10−5), four of which were located near previously characterized genes: rs756770 (ADAMTSL2), rs11782370 (SLC25A37), rs7205113 (CRISPLD2), and rs13169373 (LINC01947). A higher maximum daily buprenorphine dosage (aOR=0.98; 95%CI: 0.97, 0.995), greater number of UDS (aOR=0.97; 95%CI: 0.96, 0.99), and history of hepatitis C (HCV) infection (aOR=0.71; 95%CI: 0.57, 0.88) were associated with a reduced odds of buprenorphine response. Older age (aOR: 1.01; 95%CI: 1.000, 1.02) was associated with increased odds of buprenorphine response. This study had limited statistical power to detect genetic variants associated with a complex human phenotype like buprenorphine treatment response. Meta-analysis of multiple data sets is needed to ensure adequate statistical power for a GWAS of buprenorphine treatment response. The most robust phenotypic predictor of buprenorphine treatment response was intravenous drug use, a proxy for which was HCV infection.
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DOI：
10.1016/s0140-6736(16)00143-4
发表时间：
2016-03-12
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hou L;Heilbronner U;Degenhardt F;Adli M;Akiyama K;Akula N;Ardau R;Arias B;Backlund L;Banzato CEM;Benabarre A;Bengesser S;Bhattacharjee AK;Biernacka JM;Birner A;Brichant-Petitjean C;Bui ET;Cervantes P;Chen GB;Chen HC;Chillotti C;Cichon S;Clark SR;Colom F;Cousins DA;Cruceanu C;Czerski PM;Dantas CR;Dayer A;Étain B;Falkai P;Forstner AJ;Frisén L;Fullerton JM;Gard S;Garnham JS;Goes FS;Grof P;Gruber O;Hashimoto R;Hauser J;Herms S;Hoffmann P;Hofmann A;Jamain S;Jiménez E;Kahn JP;Kassem L;Kittel-Schneider S;Kliwicki S;König B;Kusumi I;Lackner N;Laje G;Landén M;Lavebratt C;Leboyer M;Leckband SG;Jaramillo CAL;MacQueen G;Manchia M;Martinsson L;Mattheisen M;McCarthy MJ;McElroy SL;Mitjans M;Mondimore FM;Monteleone P;Nievergelt CM;Nöthen MM;Ösby U;Ozaki N;Perlis RH;Pfennig A;Reich-Erkelenz D;Rouleau GA;Schofield PR;Schubert KO;Schweizer BW;Seemüller F;Severino G;Shekhtman T;Shilling PD;Shimoda K;Simhandl C;Slaney CM;Smoller JW;Squassina A;Stamm T;Stopkova P;Tighe SK;Tortorella A;Turecki G;Volkert J;Witt S;Wright A;Young LT;Zandi PP;Potash JB;DePaulo JR;Bauer M;Reininghaus EZ;Novák T;Aubry JM;Maj M;Baune BT;Mitchell PB;Vieta E;Frye MA;Rybakowski JK;Kuo PH;Kato T;Grigoroiu-Serbanescu M;Reif A;Del Zompo M;Bellivier F;Schalling M;Wray NR;Kelsoe JR;Alda M;Rietschel M;McMahon FJ;Schulze TG
通讯作者：
Schulze TG
影响因子：
3.9
作者：
Cox, Joseph;Allard, Robert;Small, Chris
通讯作者：
Small, Chris
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium
DOI：
10.1038/tpj.2013.30
发表时间：
2014-06
期刊：
The pharmacogenomics journal
影响因子：
--
作者：
Clarke TK;Crist RC;Ang A;Ambrose-Lanci LM;Lohoff FW;Saxon AJ;Ling W;Hillhouse MP;Bruce RD;Woody G;Berrettini WH
通讯作者：
Berrettini WH
影响因子：
4.2
作者：
Dreifuss, Jessica A.;Griffin, Margaret L.;Weiss, Roger D.
通讯作者：
Weiss, Roger D.