Identification of rs2036527 as a cis‐regulatory variant for CHRNA3 and CHRNA5 by allele‐specific expression and implications for nicotine dependence and lung cancer.
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| Title: | Identification of rs2036527 as a cis‐regulatory variant for CHRNA3 and CHRNA5 by allele‐specific expression and implications for nicotine dependence and lung cancer. |
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| Authors: | Peng, Tao (AUTHOR), Shi, Xiao‐Qian (AUTHOR), Guo, Hao (AUTHOR), Li, Hai‐Yan (AUTHOR), Zhou, Xi‐Ting (AUTHOR), Song, Hong‐Li (AUTHOR), Zhang, Xin‐Xin (AUTHOR), Fu, Wei‐Ping (AUTHOR), Sun, Chang (AUTHOR) |
| Source: | American Journal on Addictions. May2026, Vol. 35 Issue 3, p379-386. 8p. |
| Subjects: | Cis-regulatory elements (Genetics), Single nucleotide polymorphisms, Lung cancer, Genetic variation, Nicotine addiction, Forkhead transcription factors, Nicotinic acetylcholine receptors |
| Abstract: | Background and Objectives: Numerous genome‐wide association studies suggest that rs1051730 is significantly associated with nicotine dependence and further lung cancer in Caucasian. Since rs1051730 is a synonymous variant at CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit), it might be hypothesized that the causal variant might be other SNP(s) in strong linkage disequilibrium (LD). Methods: LD analysis and functional genomics work, including chromosome conformation capture (3C), luciferase assay, and chromatin immunoprecipitation (ChIP), were performed. Results: Allele‐specific expression indicates an overexpression of C allele than T at rs1051730 in lung tissues, thus verifying the hypothesis. Through LD analysis for 1000 genomes project data, 17 genetic variants are identified in strong LD with rs1051730. 3C indicates that two restrictive segments, chr15:78845145‐78852557 and chr15:78867861‐78872762, display high interaction efficiency with CHRNA3 promoter and contain two SNPs in core haplotype, rs72740964 and rs2036527, respectively. Luciferase assay suggests that only rs2036527 can alter enhancer activity. Further 3C indicates that CHRNA5 (cholinergic receptor nicotinic alpha 5 subunit) is an additional target of the enhancer containing rs2036527, which is verified by expression quantitative trait locus analysis. By ChIP, the related transcription factor, FOXA2 (forkhead box A2), is identified and their interaction is evaluated. Discussion and Conclusions: rs2036527 is the cis‐regulatory variant for CHRNA3 and CHRNA5, which can further influence nicotine dependence. Scientific Significance: This is the first report to indicate that rs2036527 genotype might be a better marker to predict the probability of developing nicotine dependence and that FOXA2, CHRNA5, and CHRNA3 might be treatment targets for nicotine dependence. [ABSTRACT FROM AUTHOR] |
| Copyright of American Journal on Addictions is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 193256893 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Identification of rs2036527 as a cis‐regulatory variant for CHRNA3 and CHRNA5 by allele‐specific expression and implications for nicotine dependence and lung cancer. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Peng%2C+Tao%22">Peng, Tao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shi%2C+Xiao‐Qian%22">Shi, Xiao‐Qian</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Guo%2C+Hao%22">Guo, Hao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Hai‐Yan%22">Li, Hai‐Yan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhou%2C+Xi‐Ting%22">Zhou, Xi‐Ting</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Song%2C+Hong‐Li%22">Song, Hong‐Li</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Xin‐Xin%22">Zhang, Xin‐Xin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fu%2C+Wei‐Ping%22">Fu, Wei‐Ping</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sun%2C+Chang%22">Sun, Chang</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22American+Journal+on+Addictions%22">American Journal on Addictions</searchLink>. May2026, Vol. 35 Issue 3, p379-386. 8p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Cis-regulatory+elements+%28Genetics%29%22">Cis-regulatory elements (Genetics)</searchLink><br /><searchLink fieldCode="DE" term="%22Single+nucleotide+polymorphisms%22">Single nucleotide polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Lung+cancer%22">Lung cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+variation%22">Genetic variation</searchLink><br /><searchLink fieldCode="DE" term="%22Nicotine+addiction%22">Nicotine addiction</searchLink><br /><searchLink fieldCode="DE" term="%22Forkhead+transcription+factors%22">Forkhead transcription factors</searchLink><br /><searchLink fieldCode="DE" term="%22Nicotinic+acetylcholine+receptors%22">Nicotinic acetylcholine receptors</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background and Objectives: Numerous genome‐wide association studies suggest that rs1051730 is significantly associated with nicotine dependence and further lung cancer in Caucasian. Since rs1051730 is a synonymous variant at CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit), it might be hypothesized that the causal variant might be other SNP(s) in strong linkage disequilibrium (LD). Methods: LD analysis and functional genomics work, including chromosome conformation capture (3C), luciferase assay, and chromatin immunoprecipitation (ChIP), were performed. Results: Allele‐specific expression indicates an overexpression of C allele than T at rs1051730 in lung tissues, thus verifying the hypothesis. Through LD analysis for 1000 genomes project data, 17 genetic variants are identified in strong LD with rs1051730. 3C indicates that two restrictive segments, chr15:78845145‐78852557 and chr15:78867861‐78872762, display high interaction efficiency with CHRNA3 promoter and contain two SNPs in core haplotype, rs72740964 and rs2036527, respectively. Luciferase assay suggests that only rs2036527 can alter enhancer activity. Further 3C indicates that CHRNA5 (cholinergic receptor nicotinic alpha 5 subunit) is an additional target of the enhancer containing rs2036527, which is verified by expression quantitative trait locus analysis. By ChIP, the related transcription factor, FOXA2 (forkhead box A2), is identified and their interaction is evaluated. Discussion and Conclusions: rs2036527 is the cis‐regulatory variant for CHRNA3 and CHRNA5, which can further influence nicotine dependence. Scientific Significance: This is the first report to indicate that rs2036527 genotype might be a better marker to predict the probability of developing nicotine dependence and that FOXA2, CHRNA5, and CHRNA3 might be treatment targets for nicotine dependence. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of American Journal on Addictions is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1111/ajad.70074 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 8 StartPage: 379 Subjects: – SubjectFull: Cis-regulatory elements (Genetics) Type: general – SubjectFull: Single nucleotide polymorphisms Type: general – SubjectFull: Lung cancer Type: general – SubjectFull: Genetic variation Type: general – SubjectFull: Nicotine addiction Type: general – SubjectFull: Forkhead transcription factors Type: general – SubjectFull: Nicotinic acetylcholine receptors Type: general Titles: – TitleFull: Identification of rs2036527 as a cis‐regulatory variant for CHRNA3 and CHRNA5 by allele‐specific expression and implications for nicotine dependence and lung cancer. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Peng, Tao – PersonEntity: Name: NameFull: Shi, Xiao‐Qian – PersonEntity: Name: NameFull: Guo, Hao – PersonEntity: Name: NameFull: Li, Hai‐Yan – PersonEntity: Name: NameFull: Zhou, Xi‐Ting – PersonEntity: Name: NameFull: Song, Hong‐Li – PersonEntity: Name: NameFull: Zhang, Xin‐Xin – PersonEntity: Name: NameFull: Fu, Wei‐Ping – PersonEntity: Name: NameFull: Sun, Chang IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 05 Text: May2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 10550496 Numbering: – Type: volume Value: 35 – Type: issue Value: 3 Titles: – TitleFull: American Journal on Addictions Type: main |
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