Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans.
Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans.
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DOI：
10.1038/s41598-021-98883-z
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发表时间：
2021-10-01
影响因子：
4.6
通讯作者：
Tyndale RF
中科院分区：
文献类型：
--
作者：
Chenoweth MJ;Cox LS;Nollen NL;Ahluwalia JS;Benowitz NL;Lerman C;Knight J;Tyndale RF
尼古丁被多态性CYP 2A 6酶灭活为可替宁，然后灭活为3′羟基可替宁。尼古丁代谢比（NMR; 3′-羟基可替宁/可替宁）是一种可遗传的尼古丁代谢生物标志物，随性别和血统而变化，并影响戒烟和疾病风险。我们在欧洲裔美国人（EA）和非洲裔美国人（AA）吸烟者中进行了NMR的性别分层全基因组关联研究（NCT 01314001，NCT 00666978）。在EA女性（n = 389）和男性（n = 541）中，（P < 5e−8）发现染色体19位点（顶部变异：rs 56113850，CYP 2A 6（内含子），对于C与T：女性：β = 0.67，P = 7.5e−22，解释了21.8%的变异;男性：β = 0.75，P = 1.2e−37，解释了26.1%的变异）。在AA女性（n = 503）和男性（n = 352）中，发现顶部变异位于19号染色体上，但因性别而异（女性：rs 11878604，CYP 2A 6（~ 16 kb 3′），C与T：β = − 0.71，P = 6.6e−26，解释了16.2%的变异;男性：rs3865454，CYP 2A 6（~ 7 kb 3′），对于G vs. T：beta = 0.64，P = 1.9e−19，解释了18.9%的变异）。在AA女性中，在12号染色体上发现了一个显著区域（顶部变异：rs 12425845：P = 5.0e−9，TMEM 132 C（~ 1 Mb 5′），解释了6.1%的变异），这在AA男性中不显著。在AA雄性中，在6号染色体（顶部变异：rs 9379805：P = 4.8e−9，SLC 17 A2（~ 8 kb 5′），解释了8.0%的变异）和16号染色体（顶部变异：rs77368288：P = 3.5e−8，ZNF 469（~ 92 kb 5′），解释了7.1%的变异）上发现了显著区域，这些区域在AA雌性中不显著。需要进一步研究19号染色体以外的这些关联，因为它们没有复制。了解性别和血统如何影响尼古丁代谢遗传学可能会改善戒烟和烟草相关疾病风险预测的个性化方法。
Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3′hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3′hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e−8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e−22, 21.8% variation explained; males: beta = 0.75, P = 1.2e−37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was found on chromosome 19 but differed by sex (females: rs11878604, CYP2A6 (~ 16 kb 3′), for C vs. T: beta = − 0.71, P = 6.6e−26, 16.2% variation explained; males: rs3865454, CYP2A6 (~ 7 kb 3′), for G vs. T: beta = 0.64, P = 1.9e−19, 18.9% variation explained). In AA females, a significant region was found on chromosome 12 (top variant: rs12425845: P = 5.0e−9, TMEM132C (~ 1 Mb 5′), 6.1% variation explained) which was not significant in AA males. In AA males, significant regions were found on chromosomes 6 (top variant: rs9379805: P = 4.8e−9, SLC17A2 (~ 8 kb 5′), 8.0% variation explained) and 16 (top variant: rs77368288: P = 3.5e−8, ZNF469 (~ 92 kb 5′), 7.1% variation explained) which were not significant in AA females. Further investigation of these associations outside of chromosome 19 is required, as they did not replicate. Understanding how sex and ancestry influence nicotine metabolism genetics may improve personalized approaches for smoking cessation and risk prediction for tobacco-related diseases.
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影响因子：
6.7
作者：
El-Boraie A;Chenoweth MJ;Pouget JG;Benowitz NL;Fukunaga K;Mushiroda T;Kubo M;Nollen NL;Sanderson Cox L;Lerman C;Knight J;Tyndale RF
通讯作者：
Tyndale RF
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
DOI：
10.1158/1055-9965.epi-14-0427
发表时间：
2014-09
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Chenoweth MJ;Novalen M;Hawk LW Jr;Schnoll RA;George TP;Cinciripini PM;Lerman C;Tyndale RF
通讯作者：
Tyndale RF
影响因子：
6.7
作者：
Fukami, T;Nakajima, M;Yokoi, T
通讯作者：
Yokoi, T