CYP2A6, MAOA, DBH, DRD4, and 5HT2A genotypes, smoking behaviour and cotinine levels in 1518 UK adolescents

Huang, Shuwen; Cook, Derek G; Hinks, Lesley J.; Chen, Xiaohe; Ye, Shu; Gilg, Julie; Jarvis, Martin J.; Whincup, Peter H; Day, Ian N.M.

doi:10.1097/01213011-200512000-00002

Cited by 54 publications

(70 citation statements)

References 47 publications

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“…Previous data on the relationship between the 5-HT 2A T102C polymorphism and smoking behavior are inconsistent. Some studies have suggested that the 5-HT 2A polymorphism is linked to cigarette smoking (do Prado-Lima et al, 2004;White et al, 2011), while others have failed to replicate this finding (Terayama et al, 2004;Huang et al, 2005). White et al (2011) reported that young Caucasian adults with the TT genotype have a greater likelihood of being a current smoker compared to the CC genotype, whereas a Brazilian study found that the CC genotype was associated with current cigarette smoking status (do Prado-Lima et al, 2004).…”

Section: Discussionmentioning

confidence: 77%

“…Postmortem brain studies have found that the C allele of T102C is associated with lower 5-HT 2A mRNA and lower protein expression compared to the T allele (Polesskaya and Sokolov, 2002). Previous studies have reported an association between the T102C polymorphism in the 5-HT 2A gene and smoking status (do PradoLima et al, 2004;White et al, 2011), but not all studies have consistently produced the same findings (Terayama et al, 2004;Huang et al, 2005). Therefore, genetic variations in 5-HT 2A among smokers require clarification.…”

Section: Introductionmentioning

confidence: 95%

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Association of HTTLPR and 5-HT2A T102C polymorphisms with smoking characteristics and anthropometric profiles of Thai males

Suriyaprom¹,

Phonrat²,

Chuensumran³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Nicotine increases serotonin release in the brain. Gene polymorphisms in the serotonergic system have been suggested to be associated with smoking behavior. We investigated a possible association between two polymorphisms in the serotonergic system -HTTLPR of a serotonin transporter gene and 5-HT 2A at position T102C -with biochemical and anthropometric parameters, and with cigarette smoking in an investigation of 200 smokers and 111 non-smokers. The two polymorphisms, HTTLPR and 5-HT 2A at position T102C, were genotyped by PCR-RFLP. They were not significantly associated with smoking status in these Thai males. Among the smokers, thiocyanate concentrations and quantity of cigarettes smoked (cigarette pack-years) were significantly higher for individuals with LL/LS genotypes than SS HTTLPR and 5-HT 2A T102C polymorphisms and smoking genotypes of 5-HTTLPR (all P < 0.05), whereas "age at starting smoking" and "duration of smoking" were not significantly different between these two genotypes. Moreover, anthropometric variables, comprising triceps skinfold thickness, arm circumference, waist circumference, hip circumference, and waist-to-hip ratio, were significantly higher for the CC/TC genotypes of 5-HT 2A than the TT genotype (all P < 0.05), except for body mass index. HTTLPR and 5-HT 2A T102C polymorphisms were not significantly associated with smoking status among Thai males; however, the HTTLPR polymorphism among smokers appears to be an indicator of increased smoking intensity consisting of cigarette packyears and thiocyanate concentrations. The 5-HT 2A T102C polymorphism plays a role in the anthropometric profiles, triceps skinfold thickness, arm circumference, waist circumference, hip circumference, and waist-to-hip ratio, but not smoking status in Thai subjects.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 95%

Association of HTTLPR and 5-HT2A T102C polymorphisms with smoking characteristics and anthropometric profiles of Thai males

Suriyaprom¹,

Phonrat²,

Chuensumran³

et al. 2012

Genet. Mol. Res.

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“…For example, the rs77905 was investigated in terms of the association with smoking status and nicotine level in 1518 adolescent subjects in United Kingdom, but no association was found. 28 Actually, Breitling et al 29 reported this rs77905 polymorphism did not influence smoking cessation programme including 577 heavy smokers.…”

Section: Discussionmentioning

confidence: 99%

Association between dopamine beta hydroxylase rs5320 polymorphism and smoking behaviour in elderly Japanese

et al. 2012

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The dopaminergic brain pathway is involved in many addictive behaviours, hence represents a good candidate in the study of smoking behaviour and nicotine addiction. Dopamine beta hydroxylase (DBH) is an enzyme that catalyses the conversion of dopamine into noradrenaline. This study, the first of its kind, was done to investigate the role of DBH rs5320 polymorphism in smoking behaviour of elderly Japanese. This was done by collecting blood samples from 2521 subjects with various smoking habits to genotype the DBH rs5320 polymorphism. Participants also had to fill out a questionnaire containing questions regarding their lifestyles. Some of the questions were from the Fagerströ m Test for Nicotine Dependence (FTND) and the Tobacco Dependence Screener (TDS). It was found that male ever-smokers with AA genotype smoked less cigarettes per day than those with GG and AG genotypes. FTND scores were also lowest in male ever-smokers with AA genotype and in female ever-smokers with AG genotype. There was no correlation detected between the TDS scores and any of the genotypes. This study shows that DBH rs5320 polymorphism influences nicotine dependence.

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“…80 In adolescents, the L-allele (seven-repeat) increased the risk of smoking and novelty seeking in males; 81 however, another study failed to replicate these findings. 82 There is modest evidence for a role of DRD1, DRD3 or DRD5 in smoking behaviors. A region near DRD1 on chromosome 5 has shown significant linkage to cigarette consumption and age of smoking initiation in genome-wide scans (Table 1); 32,40,41 one study found an association of the DdeI polymorphism in DRD1 with current smoking.…”

Section: Mk Ho and Rf Tyndale 86mentioning

confidence: 99%

“…107 In adolescents, no associations of the MAO-A VNTR polymorphisms or 1460C4T SNP were found between current, former or never smokers. 82 Catechol-O-methyltransferase is important in the degradation catecholamines, and a functional SNP (1947G4A) corresponding to Val108/158Met has been identified. Those with homozygous Val/Val genotypes have 3-4-fold higher enzyme activity compared to those with Met/Met genotypes.…”

Section: Mk Ho and Rf Tyndalementioning

confidence: 99%

Overview of the pharmacogenomics of cigarette smoking

Tyndale

2007

Pharmacogenomics J

102

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Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.

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CYP2A6, MAOA, DBH, DRD4, and 5HT2A genotypes, smoking behaviour and cotinine levels in 1518 UK adolescents

Abstract: CYP2A6 haploinsufficiency increases likelihood of continuing smoking in teenagers. We hypothesize an explanatory 'occupancy' model to explain why haploinsufficiency results in faster progression to nicotine dependence, but lower subsequent consumption.

Cited by 54 publications

References 47 publications

Association of HTTLPR and 5-HT2A T102C polymorphisms with smoking characteristics and anthropometric profiles of Thai males

Association of HTTLPR and 5-HT2A T102C polymorphisms with smoking characteristics and anthropometric profiles of Thai males

Association between dopamine beta hydroxylase rs5320 polymorphism and smoking behaviour in elderly Japanese

Overview of the pharmacogenomics of cigarette smoking

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