Archival ReportGene-Gene Interactions Among CHRNA4, CHRNB2, BDNF, and NTRK2 in Nicotine Dependence
Section snippets
Human Study Population
The subjects used in this study were of either African American (AA) or European American (EA) origin and were selected from a family study on ND, recruited primarily from the Mid-South states including Tennessee, Mississippi, and Arkansas, in the United States during 1999 to 2004 (8, 26, 27). Smokers were required to be at least 21 years of age, to have smoked for at least the last 5 years, and to have consumed an average of 20 cigarettes per day for the last 12 months. Extensive data were
Results
To determine whether gene-gene interactions exist among the four genes in affecting ND, we studied 275 unrelated smokers with an FTND score ≥4.0 and 348 unrelated nonsmokers selected from the U.S. Mid-South Tobacco Family cohort (26). Of the subjects included, the average age was 46.6 ± 13.0 for smokers and 41.6 ± 17.8 for control subjects; 70% and 78% were female subjects for smokers and control subjects, respectively; and 65% and 66% were African Americans for smokers and control subjects,
Discussion
Mounting studies have pointed to the view that genes act in concert, rather than in isolation, to affect ND. Statistical gene-gene interactions have been reported for smoking-related phenotypes for DRD2 with SLC6A3, DBH, and CYP2B6 (35, 36, 37). It has long been known that subunits α4 and β2 must assemble together to form a functional α4β2-containing heteromeric nAChR, a major highly expressed receptor type in the central nervous system. Similarly, for BDNF to exert its biological functions in
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Cited by (56)
A systematic review of genetic variation within nicotinic acetylcholine receptor genes and cigarette smoking cessation
2022, Drug and Alcohol DependenceCitation Excerpt :Furthermore, other scientific findings related to CHRNB2 and CHRNA4 indicate more investigation is necessary to determine SNP associations with smoking cessation. For example, prior studies indicate that CHRNB2 variants may not be sufficient on their own to influence nicotine addiction (Feng et al., 2004; Li et al., 2005), but may interact with variants of CHRNA4 to do so (Li et al., 2008). Moreover, nicotine dependence has been found to have a significant association with the interplay between CHRNA4 rs2236196 and CHRNB2 rs2072661 (Li et al., 2008).
Effect of 4-Fluoro-N-(4-sulfamoylbenzyl) Benzene Sulfonamide on cognitive deficits and hippocampal plasticity during nicotine withdrawal in rats
2020, Biomedicine and PharmacotherapyBrain gene expression in the context of nicotine rewards: A focus on cholinergic genes
2019, Neuroscience of Nicotine: Mechanisms and TreatmentBrain derived neurotrophic factor (BDNF), its tyrosine kinase receptor B (TrkB) and nicotine
2018, NeuroToxicologyCitation Excerpt :This is somewhat in line with the finding that almost all reported human studies of nicotine dependence found no association of the gene for the nAChR β2 subunit (CHRNB2) with nicotine dependence (Li et al., 2005; Feng et al., 2004; Silverman et al., 2000; Lueders et al., 2002) but did so for the α4 subunit gene (CHRNA4) (Li et al., 2005; Feng et al., 2004; Hutchison et al., 2007). Subsequent analysis showed a strong interaction of CHRNA4 with BDNF and CHRNB2 with TrkB (Li et al., 2008). Non-homology in BDNF and nAChRs expression changes have also been reported.
Tyrosine receptor kinase B gene variants (NTRK2 variants) are associated with depressive disorders in temporal lobe epilepsy
2017, Epilepsy and BehaviorCitation Excerpt :The NTRK2 gene codes the TrkB receptor [21]. NTRK2 variants have been associated with neurological or psychiatric disorders such as mood disorders [22], vulnerability to nicotine dependence or alcohol abuse [23,24], obsessive–compulsive disorder [25], attention-deficit/hyperactivity disorder [26], autism [27], and Alzheimer disease [28]. Depression is a very common psychiatric comorbidity in TLE with an important impact on the quality of life of patients [1–4,29,30].