The significant association of BDNF variants with ND implies that this gene plays a role in the etiology of ND in EAs and that its involvement is gender specific.
In summary, our findings provide convincing evidence for the involvement of the nAChR alpha4 subunit, but not of the nAChR beta2 subunit, in nicotine addiction.
The initial pharmacogenetic studies of pharmacotherapies approved by the United States Food and Drug Administration for treatment of nicotine dependence-nicotine replacement (nicotine gum, nicotine nasal spray, and transdermal nicotine) and bupropion-have identified candidate alleles at the dopamine D2 receptor gene and mu opioid receptor gene that may predict therapeutic response.
Our data suggest that a decreased expression of the gene encoding the 5-HTT transporter, due to "S" promoter polymorphism, may be associated with smoking behavior among adolescents and increased risk to develop nicotine dependence, possibly in relationship to personality traits, temperamental characteristics, and school under-achievements.
In summary, our findings provide the first evidence for the involvement of DDC in the susceptibility to ND and, further, reveal the racial specificity of its impact.
Given the biological role of the neuronal nicotinic acetylcholine receptors and the substantial comorbidity of nicotine dependence in psychiatric disorders, the CHRNA2 gene is a plausible candidate gene for bipolar disorder (BPD).
We analyzed genetic variants of the promoter region of the cholecystokinin (CCK; which modulates the release of dopamine) gene, and intron 1 and exon 5 of the CCKA receptor gene, and performed association analyses of nicotine dependence using an allele-specific amplification (ASA) method and PCR-RFLP methods.
We have analyzed seven DNA polymorphisms located in the genomic region of SLC18A2 for association with alcohol- and nicotine dependence, using a family-based design.
For severity of nicotine dependence, two SNPs in CHRNA7 (rs1909884 and rs883473), one SNP in CHRNA5 (rs680244) and the interaction of a SNP in CHRNA7 (rs2337980) with neuroticism, were included in the model (P=2.24 x 10(-7), Nagelkerke r(2)=0.40).
There was relatively weak evidence for association of the flanking DRD2 and NCAM1 markers to ND, but very strong evidence of association of multiple SNPs at TTC12 and ANKK1 in both populations (minimal P=0.0007 in AAs and minimal P=0.00009 in EAs), and in the pooled sample, as well as strong evidence for highly significant association of a single haplotype spanning TTC12 and ANKK1 to ND in the pooled sample (P=0.0000001).
We investigated the association between smoking behavior and genetic variations in the D2 dopamine receptor (DRD2), which mediates nicotine dependence.
For severity of nicotine dependence, two SNPs in CHRNA7 (rs1909884 and rs883473), one SNP in CHRNA5 (rs680244) and the interaction of a SNP in CHRNA7 (rs2337980) with neuroticism, were included in the model (P=2.24 x 10(-7), Nagelkerke r(2)=0.40).
We found nominally significant (P<0.05) allelic and genotypic association with smoking initiation of SNP rs2072660 and multilocus haplotypes (P<0.007-0.05) in CHRNB2 and nominal (P<0.05) allelic or genotypic association of SNPs in CHRNA7 (rs1909884), CHRNA9 (rs4861065) and CHRNB3 (rs9298629) with nicotine dependence.
In summary, our results provide evidence for a role of COMT in the susceptibility to ND and further confirm that its effect is ethnic and gender specific.
We found nominally significant (P<0.05) allelic and genotypic association with smoking initiation of SNP rs2072660 and multilocus haplotypes (P<0.007-0.05) in CHRNB2 and nominal (P<0.05) allelic or genotypic association of SNPs in CHRNA7 (rs1909884), CHRNA9 (rs4861065) and CHRNB3 (rs9298629) with nicotine dependence.
To demonstrate the more powerful method, we re-analyzed an existing dataset, which confirmed the association of the DOPA decarboxylase (DDC) gene on chromosome 7p11 with measures of nicotine dependence.
In conclusion, there is an important association between MAOA polymorphisms and smoking status, suggesting a possible role of MAOA gene variants in nicotine dependence.