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Gamma-aminobutyric acid receptor genes and nicotine dependence: evidence for association from a case–control study.

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Title: Gamma-aminobutyric acid receptor genes and nicotine dependence: evidence for association from a case–control study.
Authors: Agrawal, Arpana (AUTHOR), Pergadia, Michele L. (AUTHOR), Saccone, Scott F. (AUTHOR), Hinrichs, Anthony L. (AUTHOR), Lessov‐Schlaggar, Christina N. (AUTHOR), Saccone, Nancy L. (AUTHOR), Neuman, Rosalind J. (AUTHOR), Breslau, Naomi (AUTHOR), Johnson, Eric (AUTHOR), Hatsukami, Dorothy (AUTHOR), Montgomery, Grant W. (AUTHOR), Heath, Andrew C. (AUTHOR), Martin, Nicholas G. (AUTHOR), Goate, Alison M. (AUTHOR), Rice, John P. (AUTHOR), Bierut, Laura J. (AUTHOR), Madden, Pamela A. F. (AUTHOR)
Source: Addiction. Jun2008, Vol. 103 Issue 6, p1027-1038. 12p. 1 Diagram, 4 Charts.
Subjects: GABA receptors, Nicotine addiction, Genetic polymorphisms, Smoking, Drug addiction, Logistic regression analysis, Genetics
Abstract: Aims The gamma-aminobutyric acid receptor A ( GABRA) gene clusters on chromosomes 4 and 5 have been examined previously for their association with alcohol and drug dependence phenotypes. Compelling evidence suggests that GABRA2 is associated with alcohol and drug dependence. However, no study has investigated whether genes in the GABAA gene clusters are associated with nicotine dependence, an important phenotype with a high correlation to persistent smoking, the single most preventable cause of mortality world-wide. Design Using data on 1050 nicotine-dependent cases and 879 non-dependent smoking controls, we used logistic regression to examine the association between single nucleotide polymorphisms (SNPs) in 13 genes in the GABAA receptor system as well as GABBR2 (a GABAB gene). Findings We found evidence for association between four SNPs in GABRA4, two SNPs in GABRA2 and one SNP in GABRE with nicotine dependence. These included a synonymous polymorphism in GABRA2 (rs279858), lying in a highly conserved region, which has been shown previously to be associated with alcohol and drug dependence. A non-synonymous polymorphism (rs16859834/rs2229940) in GABRA4, also highly conserved, was associated at P-value of 0.03. Significant haplotypes associated with nicotine dependence were found for GABRA2. No evidence for epistatic interactions were noted. Our study did not find evidence for an association between GABBR2 gene and nicotine dependence. Conclusions Given the potential role of compounds that enhance GABAergic neurotransmission in smoking cessation research, these findings have enormous potential for informing the wider field of addiction research. [ABSTRACT FROM AUTHOR]
Copyright of Addiction 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.)
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  Data: Gamma-aminobutyric acid receptor genes and nicotine dependence: evidence for association from a case–control study.
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  Data: <searchLink fieldCode="AR" term="%22Agrawal%2C+Arpana%22">Agrawal, Arpana</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pergadia%2C+Michele+L%2E%22">Pergadia, Michele L.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Saccone%2C+Scott+F%2E%22">Saccone, Scott F.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hinrichs%2C+Anthony+L%2E%22">Hinrichs, Anthony L.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lessov‐Schlaggar%2C+Christina+N%2E%22">Lessov‐Schlaggar, Christina N.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Saccone%2C+Nancy+L%2E%22">Saccone, Nancy L.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Neuman%2C+Rosalind+J%2E%22">Neuman, Rosalind J.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Breslau%2C+Naomi%22">Breslau, Naomi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Johnson%2C+Eric%22">Johnson, Eric</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hatsukami%2C+Dorothy%22">Hatsukami, Dorothy</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Montgomery%2C+Grant+W%2E%22">Montgomery, Grant W.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Heath%2C+Andrew+C%2E%22">Heath, Andrew C.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Martin%2C+Nicholas+G%2E%22">Martin, Nicholas G.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Goate%2C+Alison+M%2E%22">Goate, Alison M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rice%2C+John+P%2E%22">Rice, John P.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bierut%2C+Laura+J%2E%22">Bierut, Laura J.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Madden%2C+Pamela+A%2E+F%2E%22">Madden, Pamela A. F.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Addiction%22">Addiction</searchLink>. Jun2008, Vol. 103 Issue 6, p1027-1038. 12p. 1 Diagram, 4 Charts.
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  Data: Aims The gamma-aminobutyric acid receptor A ( GABRA) gene clusters on chromosomes 4 and 5 have been examined previously for their association with alcohol and drug dependence phenotypes. Compelling evidence suggests that GABRA2 is associated with alcohol and drug dependence. However, no study has investigated whether genes in the GABAA gene clusters are associated with nicotine dependence, an important phenotype with a high correlation to persistent smoking, the single most preventable cause of mortality world-wide. Design Using data on 1050 nicotine-dependent cases and 879 non-dependent smoking controls, we used logistic regression to examine the association between single nucleotide polymorphisms (SNPs) in 13 genes in the GABAA receptor system as well as GABBR2 (a GABAB gene). Findings We found evidence for association between four SNPs in GABRA4, two SNPs in GABRA2 and one SNP in GABRE with nicotine dependence. These included a synonymous polymorphism in GABRA2 (rs279858), lying in a highly conserved region, which has been shown previously to be associated with alcohol and drug dependence. A non-synonymous polymorphism (rs16859834/rs2229940) in GABRA4, also highly conserved, was associated at P-value of 0.03. Significant haplotypes associated with nicotine dependence were found for GABRA2. No evidence for epistatic interactions were noted. Our study did not find evidence for an association between GABBR2 gene and nicotine dependence. Conclusions Given the potential role of compounds that enhance GABAergic neurotransmission in smoking cessation research, these findings have enormous potential for informing the wider field of addiction research. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Addiction 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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