Association and interaction analyses of GABBR1 and GABBR2 with nicotine dependence in European- and African-American populations

Li, Ming D., Mangold, Jamie E., Seneviratne, Chamindi, Chen, Guo-Bo, Ma, Jennie Z., Lou, Xiang-Yang and Payne, Thomas J. (2009) Association and interaction analyses of GABBR1 and GABBR2 with nicotine dependence in European- and African-American populations. PLoS One, 4 9: e7055.1-e7055.11. doi:10.1371/journal.pone.0007055


Author Li, Ming D.
Mangold, Jamie E.
Seneviratne, Chamindi
Chen, Guo-Bo
Ma, Jennie Z.
Lou, Xiang-Yang
Payne, Thomas J.
Title Association and interaction analyses of GABBR1 and GABBR2 with nicotine dependence in European- and African-American populations
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2009-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1371/journal.pone.0007055
Open Access Status DOI
Volume 4
Issue 9
Start page e7055.1
End page e7055.11
Total pages 12
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Formatted abstract
Previous studies have demonstrated that the γ-aminobutyric acid type B (GABAB) receptor plays an essential role in modulating neurotransmitter release and regulating the activity of ion channels and adenyl cyclase. However, whether the naturally occurring polymorphisms in the two GABAB receptor subunit genes interact with each other to alter susceptibility to nicotine dependence (ND) remains largely unknown. In this study, we genotyped 5 and 33 single nucleotide polymorphisms (SNPs) for GABAB receptor subunit 1 and 2 genes (GABBR1, GABBR2), respectively, in a sample of 2037 individuals from 602 nuclear families of African- American (AA) or European-American (EA) origin. We conducted association analyses to determine (1) the association of each subunit gene with ND at both the individual SNP and haplotype levels and (2) the collective effect(s) of SNPs in both GABAB subunits on the development of ND. Several individual SNPs and haplotypes in GABBR2 were significantly associated with ND in both ethnic samples. Two haplotypes in AAs and one haplotype in EAs showed a protective effect against ND, whilst two other haplotypes in AAs and three haplotypes in EAs showed a risk effect for developing ND. Interestingly, these significant haplotypes were confined to two regions of GABBR2 in the AA and EA samples. Additionally, we found two minor haplotypes in GABBR1 to be positively associated with Heaviness of Smoking Index (HSI) in the EA sample. Finally, we demonstrated the presence of epistasis between GABBR1 and GABBR2 for developing ND. The variants of GABBR1 and GABBR2 are significantly associated with ND, and the involvement of GABBR1 is most likely through its interaction with GABBR2, whereas GABBR2 polymorphisms directly alter susceptibility to ND. Future studies are needed with more dense SNP coverage of GABBR1 and GABBR2 to verify the epistatic effects of the two subunit genes.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes For ERA

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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