A genetic association for cigarette smoking behavior.

Abstract

Dopaminergic genes are likely candidates for heritable influences on cigarette smoking. In an accompanying article, Lerman et al. (1999) report associations between allele 9 of a dopamine transporter gene polymorphism (SLC6A3-9) and lack of smoking, late initiation of smoking, and length of quitting attempts. The present investigation extended their study by examining both smoking behavior and personality traits in a diverse population of nonsmokers, current smokers, and former smokers (N = 1,107). A significant association between SLC6A3-9 and smoking status was confirmed and was due to an effect on cessation rather than initiation. The SLC6A3-9 polymorphism was also associated with low scores for novelty seeking, which was the most significant personality correlate of smoking cessation. It is hypothesized that individuals carrying the SLC6A3-9 polymorphism have altered dopamine transmission, which reduces their need for novelty and reward by external stimuli, including cigarettes.

Overview of the pharmacogenomics of cigarette smoking

“…88,93 The SLC6A3-9 allele has been associated with a lower risk of current smoking and starting smoking before age 16 years, longer periods of abstinence during previous quit attempts and increased quitting. 94,95 However, these findings have not been replicated, 96,97 and conversely, the SCL6A3-9 allele has also been associated with stronger cue-or stress-induced cravings. 68 Examination of a single-nucleotide polymorphism (SNP) in the 3 0 -UTR of SCL6A3-9 (rs27072G4A) found individuals with the A-allele were more likely to initiate smoking before age 18 years.…”

Polymorphisms in the 3′-untranslated region of human and monkey dopamine transporter genes affect reporter gene expression

“…With the exception of a small (Ͻ4%) but significant association between 10-repeat length alleles in the 3Ј-UTR and ADHD, [29][30][31][32][33] analysis of DAT alleles based on the number of repeat sequences (length) of the VNTR has yielded negative or inconsistent data. 41,45,[48][49][50][51][52][53][54][55][56] In view of mounting evidence that the 3Ј-UTR of genes may contribute to gene expression, 57,58 we and others extended the search for variability in primate DAT genes beyond length, to SNPs in the 3Ј-UTR. [22][23][24]44,45 We identified a 3Ј-UTR of a human 10-repeat DAT allele containing a novel SNP that altered a DraI restriction site (DraI−).…”

“…Less consistently, alleles with the 9-repeat length have been associated with cocaine-induced paranoia and alcohol or nicotine addictions. [35][36][37][38][39][40][41][42] Emergent from these findings is whether the number Figure 1 Schematic representation of the human dopamine transporter gene. Shaded exons in the DNA form the coding region, white exons contribute to the 5Ј and 3Ј non-coding regions.…”

Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data

“…A total of 28 studies published between 1994 and 2007, comprising k = 34 independent samples, were identifi ed by the search strategy, met the inclusion criteria, and contributed to the metaanalysis ( Bierut et al, 2000 ;Comings et al, 1996Comings et al, , 1997Connor et al, 2007 ;Costa-Mallen et al, 2000 ;David et al, 2007 ;Erblich, Lerman, Self, Diaz, & Bovbjerg, 2004Freire, Marques, Hutz, & Bau, 2006 ;Hamajima et al, 2002 ;Johnstone, Yudkin, Griffi ths, et al, 2004 ;Lee, 2003 ;Lerman et al, 1999Lerman et al, , 2003Morton et al, 2006 ;Noble et al, 1994 ;Preuss, Zill, Koller, Bondy, & Sokya, 2007 ;Qi, Tan, Xing, Miao, & Lin, 2002 ;Robinson et al, 2006 ;Sabol et al, 1999 ;Singleton et al, 1998 ;Spitz et al, 1998 ;Swan et al, 2005 ;Timberlake et al, 2007 ;Ton et al, 2007 ;Wu, Hudmon, Detry, Chamberlain, & Spitz, 2000 ;Yoshida et al, 2001 ). Data from the present study also were included in the meta-analysis.…”