Genetic clues to the molecular basis of tobacco addiction and progress towards personalized therapy

Walton, Robert; Johnstone, Elaine; Munafò, Marcus R.; Neville, Matt J.; Griffiths, Sian

doi:10.1016/s1471-4914(01)01915-3

Cited by 50 publications

(43 citation statements)

References 43 publications

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“…The strongest evidence linking particular alleles to nicotine addiction comes from studies on genetic variation in the dopaminergic system, in cytochrome P450 enzymes, the serotonin transporter gene and monoamine oxidase. 9,10 None of these genes is located on chromosomes 3, 6, 10 or 14. However, most genes that play a major role in tobacco addiction are not yet known.…”

Section: Discussionmentioning

confidence: 99%

“…Association studies point to dopamine receptor genes, dopamine transporter genes, cytochrome P450 and serotonergic genes. 9,10 Association studies have relatively high statistical power, and can detect quantitative trait loci (QTLs) with only small effects. A possible disadvantage of the candidate gene approach is that the focus is on known pathways, which may lead us to overlook genes that are etiologically important, because of our ignorance of other biological systems involved.…”

Section: Introductionmentioning

confidence: 99%

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Linkage analysis of smoking initiation and quantity in Dutch sibling pairs

et al. 2004

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The heritability of smoking initiation (SI) and number of cigarettes smoked (NC) was determined in 3657 Dutch twin pairs. For SI a heritability of 36% was found and for NC of 51%. Both SI and NC were also significantly influenced by environmental factors shared by family members. The etiological factors that influence these traits partly overlap. Linkage analyses were performed on data of 536 DZ twins and siblings from 192 families, forming 592 sibling pairs. Results suggested QTLs on chromosome 6 (LOD ¼ 3.05) and chromosome 14 (LOD ¼ 1.66) for SI and on chromosome 3 (LOD ¼ 1.98) for NC. Strikingly, on chromosome 10 a peak was found in the same region for both SI (LOD ¼ INTRODUCTIONLarge-scale population-based twin and family studies have shown that genetic factors contribute to individual differences in smoking behavior. 1-4 Several different, possibly correlated, dimensions of smoking behavior can be distinguished: smoking initiation (SI), number of cigarettes smoked per day and nicotine dependence (ND). 5 Koopmans et al 6 investigated the heritability of SI and the number of cigarettes smoked per day (NC) in adolescent Dutch twins by considering a single liability model, an independent liability model and a combined model. The combined model best described the data and showed that 39% of the variance in SI and 86% of the variance in NC was explained by genetic influences. Kendler et al 7 found that liabilities to SI and ND were substantially correlated but not identical, and that heritable factors played an important role in both SI and in ND.The next step after obtaining evidence for significant heritability is to identify chromosomal regions involved in smoking behavior, either by linkage or association approaches. 8 Both human and animal studies have explored candidate genes for smoking behavior. Association studies point to dopamine receptor genes, dopamine transporter genes, cytochrome P450 and serotonergic genes. 9,10 Association studies have relatively high statistical power, and can detect quantitative trait loci (QTLs) with only small effects. A possible disadvantage of the candidate gene approach is that the focus is on known pathways, which may lead us to overlook genes that are etiologically important, because of our ignorance of other biological systems involved. In contrast, linkage analysis will identify chromosomal regions that harbor known and

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Linkage analysis of smoking initiation and quantity in Dutch sibling pairs

et al. 2004

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“…DRD2 and CYP2B6 are but two of the many candidate genes implicated in the relevant biological pathways directly involved in the 'reward deficit syndrome' (see, for example, Walton et al 50 ) and bupropion response. Therapeutic response is likely to be the result of the interaction between several metabolic and receptor genes.…”

Section: Ge Swan Et Almentioning

confidence: 99%

Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment with bupropion SR

et al. 2004

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The A1 allele of the dopamine D2 receptor gene (DRD2) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior. In a study of smokers enrolled in an open-label, randomized effectiveness trial, we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling. Adherence to treatment and pointprevalent smoking status were assessed at 3 and 12 months, respectively, following a target quit date. Compared to women who carry both A2 alleles, women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects (odds ratio (OR) ¼ 1.91, 95% confidence interval (CI) ¼ 1.01-3.60; Po0.04) and at 12 months were somewhat more likely to report smoking (OR ¼ 0.76, 95% CI ¼ 0.56-1.03; Po0.076). Significant associations or trends were not observed in men. In women, individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function. INTRODUCTIONTobacco use remains the major preventable cause of premature disability and death in developed countries. Despite best efforts to date, 46 million people still smoke in the United States, and over 440 000 people die each year from tobaccorelated illness; the estimated smoking-related cost to the economy is $157 billion annually.1 Effective pharmacologic interventions for smoking cessation include several forms of nicotine replacement and the use of the antidepressant medication, bupropion.2 Despite treatment advances, smoking relapse after successful intervention for smoking cessation occurs in 70 to 80% of patients within 12 months. [3][4][5] Still to be determined is why some people remain nonsmokers after pharmacologic intervention and others do not.The dopaminergic mesocorticolimbic pathway in the brain is thought to play an important role in tobacco and nicotine addiction. [6][7][8] The TaqIA polymorphism of the dopamine D2 receptor gene (DRD2) results from a C/T

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“…The cognitive-affective consequences of smoking, such as pleasure, better concentration, and better tolerance of acute stress, are thought to be rewarding and in this way reinforce the smoking habit (Balfour, 2004;Walton et al, 2001). Smoking is also thought to be conditioned to external stimuli such as environment and social context, and to internal stimuli such as stress, tiredness and hunger (Perkins, 1999;Haustein, 2003).…”

Section: Introductionmentioning

confidence: 99%

The Nicotine Dependence Syndrome Scale in Finnish smokers

Broms

Madden

Heath

et al. 2007

Drug and Alcohol Dependence

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The Nicotine Dependence Syndrome Scale (NDSS) is a new multidimensional measure of nicotine dependence. The study aim was to examine the structure and heritability of the NDSS and its associations with nicotine dependence defined by FTND and DSM-IV criteria among Finnish smokers participating in an ongoing twin-family study. Adult twin pairs concordant for smoking from the Finnish Twin Cohort Study, and their siblings and parents were interviewed. Among 1370 smokers, the NDSS sum score (a summary measure of dependence) correlated moderately high with FTND score (r=0.62). Subjects in the highest NDSS sum score groups were more likely to be nicotine dependent according to DSM-IV criteria compared with those in the lowest quintile (odds ratio = 36.7, 95% Confidence interval 13.0-103). In exploratory factor analysis we derived three factors, named drive/priority, stereotypy/continuity and tolerance. The drive/priority factor correlated best with FTND (r=0.54). Genetic modelling showed no differences in the genetic architecture of NDSS or FTND by gender; the overall heritability estimate for NDSS was 0.30 (95% CI 0.06-0.47), and for FTND 0.40 (95% CI 0.23-0.55)The NDSS sum score is moderately high associated with DSM-IV nicotine dependence as well as FTND. These analyses indicate that the NDSS functions well in a Finnish family-based sample and provide additional validation of a new scale developed to capture complex behavioral features of nicotine dependence.

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Genetic clues to the molecular basis of tobacco addiction and progress towards personalized therapy

Cited by 50 publications

References 43 publications

Linkage analysis of smoking initiation and quantity in Dutch sibling pairs

Linkage analysis of smoking initiation and quantity in Dutch sibling pairs

Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment with bupropion SR

The Nicotine Dependence Syndrome Scale in Finnish smokers

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