期刊论文详细信息
BMC Genetics
SLC6A4 STin2 VNTR genetic polymorphism is associated with tobacco use disorder, but not with successful smoking cessation or smoking characteristics: a case control study
Sandra Odebrecht Vargas Nunes3  Maria Angelica Ehara Watanabe4  Michael Berk1  Seetal Dodd1  Luiz Gustavo Piccoli de Melo3  Mateus Medonça Vargas3  Heber Odebrecht Vargas3  Edna Maria Vissoci Reiche2  Carolina Batista Ariza4  Roberta Losi Guembarovski4  Michael Maes5  Márcia Regina Pizzo de Castro3 
[1] Barwon Health and the Geelong Clinic, Swanston Centre, Geelong, Victoria 3220, Australia;Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Canter, Londrina State University, Londrina, Paraná, Brazil;Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, Campus Universitário/Cx, Postal 600, Londrina, Paraná ZIP 86051-990, Brazil;Department of Pathological Sciences, Biological Sciences Centre, Londrina State University, Londrina, Paraná, Brazil;Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil
关键词: Genetic;    Polymorphism;    Oxidative stress;    Inflammation;    Serotonin;    Smoking cessation;    Tobacco use disorder;    STin2 VNTR;   
Others  :  869614
DOI  :  10.1186/1471-2156-15-78
 received in 2013-12-10, accepted in 2014-06-18,  发布年份 2014
PDF
【 摘 要 】

Background

The aim of this study was to determine if variable number of tandem repeats (VNTR) in the second intron (STin2) of the serotonin transporter (SLC6A4) gene was associated with tobacco use disorder, successful smoking cessation, or smoking characteristics. In this case–control study, patients with current tobacco use disorder, diagnosed according to DSM IV criteria (n = 185), and never-smokers, diagnosed according to CDC criteria (n = 175), were recruited and received 52 weeks of combined pharmacotherapy and cognitive therapy. Successful smoking cessation was defined as exhaled carbon monoxide < 6 ppm. SLC6A4 gene STin2 VNTR polymorphism was assessed using a Multiplex-PCR-based method. At baseline, participants were evaluated using the Fagerström Test for Nicotine Dependence (FTND) and the ASSIST scale.

Results

The STin2.12 allele (OR = 2.45; 95% CI = 1.44-4.15, p < 0.001) was associated with an increased risk for tobacco use disorder, while the STin2.10/10 genotype (OR = 0.42; 95% CI 0.25-0.71, p < 0.001) decreased risk. There were no significant associations between tobacco use disorder and the STin2.10 or STin2.9 alleles or the other genotypes (STin2.12/12, 12/10, 12/9, 10/9 or 9/9). There were no significant associations between the STin2 genotypes and alleles and successful smoking cessation, smoking characteristics and increased alcohol or sedative use risk.

Conclusions

Our results suggest that the STin2.10/10 genotype and STin2.12 allele are associated with tobacco use disorder or nicotine dependence, but not with treatment response or severity of dependence. It is hypothesized that the ST2in.12 allele by modulating the metabolism of serotonin may participate in the pathophysiology of tobacco use disorder or nicotine dependence.

【 授权许可】

   
2014 Pizzo de Castro et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140730021320357.pdf 214KB PDF download
【 参考文献 】
  • [1]Ezzati M, Lopez AD: Estimates of global mortality attributable to smoking 2000. Lancet 2003, 362:847-852.
  • [2]Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray C: Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006, 367:1747-1757.
  • [3]Belsky D, Moffitt T, Baker T, Biddlem A, Evans J, Harrington H, Houts R, Meier M, Sugden K, Williams B, Poulton R, Caspi A: Polygenic risk and the developmental progression to heavy, persistent smoking and nicotine dependence. JAMA Psychiatry 2013, 70(5):534-542.
  • [4]Centers for Disease Control and Prevention (CDC): Quitting smoking among adults: United States, 2001–2010. Morb Mortal Wkly Rep 2011, 60(44):1513-1519.
  • [5]American Psychiatric Association: Diagnostic and statistical manual of mental disorders: DSM-5. 5th edition. Washington, DC: Author, American Psychiatric Publishing; 2013.
  • [6]Serretti A, Calati R, Mandelli L, De Ronchi D: Serotonin transporter gene variants and behavior: a comprehensive review. Curr Drug Targets 2006, 7:1659-1669.
  • [7]Alves de Lima K, Guembarovski R, Oda J, Ramos G, Oliveira B, Cavalli I, Ribeiro E, Gonçalves M, Aoki M, Nunes SOV, Watanabe MAE: Association between the STin2 VNTR polymorphism and smoking behavior in oral cancer patients and healthy individuals. Clin Exp Med 2012, 12:13-19.
  • [8]Brody LC, Hamer HD, Haaga DAF: Depression vulnerability, cigarette smoking, and the serotonin transporter gene. Addict Behav 2005, 30:557-566.
  • [9]Tsuang MT, Francis T, Minor K, Thomas A, Stone WS: Genetics of smoking and depression. Hum Genet 2012, 131(6):905-915.
  • [10]Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, Mc Clay J, Mill J, Martin J, Braithwaite A, Poulton R: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003, 301:386-389.
  • [11]Lerman C, Caparaso N, Audrain J, Main D, Boyd N, Shields P: Interacting effects of the serotonin transporter gene and neuroticism in smoking practices and nicotine dependence. Mol Psychiatry 2000, 5:189-192.
  • [12]Lerman C, Shields P, Audrain J, Main D, Cobb B, Boyd N, Caparaso N: The role of the serotonin transporter gene in cigarette smoking. Cancer Epidemiol Biomarkers Prev 1998, 7:253-255.
  • [13]Ishikawa H, Ohtsuki T, Ishiguro H, Yamakawa-Kobayashi K, Endo K, Lin Y-L, Yanagi H, Tsuchiya S, Kawata K-i, Hamaguchi H, Arinami T: Association between serotonin transporter gene polymorphism and smoking japonese males. Cancer Epidemiol Biomarkers Prev 1999, 8:831-833.
  • [14]Hu S, Brody CL, Fisher C, Gunzerath L, Nelson ML, Sabol SZ, Sirota LA, Marcus SE, Greenberg BD, Murphy DL, Hamer DH: Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior. Mol Psychiatry 2000, 5(2):181-188.
  • [15]Nunes SOV, De Castro MRP, Vargas HO, Vargas MM, Bueno RRM, Fonseca ICB, Dodd S, Berk M: Clinical characteristics and smoking cessation: an analysis of sex and depressive disorders differences. Addict Disord Their Treat 2013, 12(3):158-165.
  • [16]Munafò MR, Johnstone EC, Mackintosh B: Association of serotonin transporter genotype with selective processing of smoking-related stimuli in current smokers and ex-smokers. Nicotine Tob Res 2005, 7(5):773-778.
  • [17]Munafò MR, Johnstone EC, Wileyto EP, Shields PG, Elliot KM, Lerman C: Lack of association of 5-HTTLPR genotype with smoking cessation in a nicotine replacement therapy randomized trial. Cancer Epidemiol Biomarkers Prev 2006, 15(2):398-400.
  • [18]Skowronek MH, Laucht M, Hohm E, Becker K, Schmidt M: Interaction between the dopamine D4 receptor and the serotonin transporter promoter polymorphisms in alcohol and tobacco use among 15-year- olds. Neurogenetics 2006, 7:239-246.
  • [19]Trummer O, Köppel H, Wascher TC, Grünbacher G, Gutjahr M, Stanger O, Ramschak-Schwarzer S, Boehm BO, Winkelmann BR, März W, Renner W: The serotonin transporter gene polymorphism is not associated with smoking behavior. Pharmacogenomics J 2006, 6:397-400.
  • [20]David SP, Munafò MR, Murphy MFG, Walton RT, Johnstone EC: The serotonin transporter 5- HTTLPR polymorphism and treatment response to nicotine patch: Follow-up of a randomized controlled trial. Nicotine Tob Res 2007, 9(2):225-231.
  • [21]Han D-H, Joe K-H, Na C, Lee Y-S: Effect of genetic polymorphisms on smoking cessation: a trial of bupropion in korean male smokers. Psychiatr Genet 2008, 18:11-16.
  • [22]Sieminska A, Buczkowski K, Jassen E, Tkacz E: Lack of association between serotonin transporter gene polymorphism 5- HTTLPR and smoking among Polish population: a case–control study. BMC Med Genet 2008, 9:76.
  • [23]Watanabe MAE, Nunes SOV, Amarante MK, Guembarovski RL, Oda JMM, Lima KWAD, Fungaro MHP: Genetic polymorphism of serotonin transporter 5-HTTLPR: involvement in smoking behaviour. J Genet 2011, 90:179-185.
  • [24]Ishii T, Wakabayashi R, Kurosaki H, Gemma A, Kida K: Association of serotonin transporter gene variation with smoking, chronic obstructive pulmonary disease, and its depressive symptoms. Am J Hum Genet 2011, 56:41-46.
  • [25]Yang Z, Seneviratne C, Wang S, Ma JZ, Payene TJ, Wang J, Li MD: Serotonin transporter and receptor genes significantly impact nicotine dependence through genetic interactions in both european american and african smokers. Drug Alcohol Depend 2013, 129:217-225.
  • [26]Kremmer I, Bachner-Melman R, Reshef A, Broude L, Nemanov L, Gritsenko I, Heresco-Levy U, Elizur Y, Ebstein RP: Association of the serotonin transporter gene with smoking behavior. Am J Psychiatry 2005, 162(5):924-930.
  • [27]Mrazek DA: Psychiatric Pharmacogenomics. New York: Oxford University Press; 2010.
  • [28]Herman A, Balogh K: Polymorphisms of the serotonin transporter and receptor genes: susceptibility to substance abuse. Subst Abuse Rehabil 2012, 20(2–3):49-57.
  • [29]Iordanidou M, Tavridou A, Petridis I, Kyroglou S, Kaklamanis L, Christakidis D, Manolopoulos VG: Association of polymorphisms of the serotonergic system with smoking initiation in Caucasians. Drug Alcohol Depend 2010, 108:70-76.
  • [30]Sarosi A, Gonda X, Balogh G, Domotor E, Szekely A, Hejjas K, Sasvari-Szekely M, Faludi G: Association of the STin2 polymorphism of the serotonin transporter gene with a neurocognitive endophenotype in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2008, 32:1667-1672.
  • [31]Fan JB, Scalar P: Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia. Mol Psychiatry 2005, 10:928-938.
  • [32]Castro MRP, Matsuo T, Nunes SOV: Clinical characteristics and quality of life of smokers at a referral center for smoking cessation. J Bras Pneumol 2010, 36(1):67-74.
  • [33]Castro MRP, Matsuo T, Nunes SOV: Characteristics of smokers in smoking cessation interventions: an analysis of sex differences. Addict Disord Their Treat 2010, 9(4):135-142.
  • [34]Nunes SOV, Vargas HO, Brum J, Prado E, Vargas MM, De Castro MRP, Dodd S, Berk M: A comparison of inflammatory markers in depressed and non-depressed smokers. Nicotine Tob Res 2012, 14:540-546.
  • [35]Vargas HO, Nunes SOV, De Castro MRP, Bortolasci CC, Barbosa DS, Morimoto HK, Venugopal K, Dodd S, Maes M, Berk M: Oxidative stress and lowered total antioxidant status are associated with history of suicide attempts. J Affect Disordersin press
  • [36]Vargas HO, Nunes SOV, De Castro MRP, Vargas MM, Barbosa DS, Bortolasci CC, Venugopal K, Dodd S, Berk M: Oxidative stress and inflammatory markers are associated with depression and nicotine dependence. Neurosci Lett 2013, 544:136-140.
  • [37]Malone KM, Waternaux C, Haas GL, Cooper TB, Li S, Mann JJ: Cigarette smoking, suicidal behavior, and serotonin function in major psychiatric disorders. Am J Psychiatry 2003, 160:773-779.
  • [38]Bah J, Lindström M, Westberg L, Mannerås L, Ryding E, Henningsson S, Melke J, Rosén I, Träskman-Bendz L, Erikson E: Serotonin transporter gene polymorphisms: effects on serotonin transporter availability in the brain of suicide attempters. Psychiatry Res 2008, 162:221-229.
  • [39]Quaak M, Schayck CP, Knaapen AM, Schooten F: Genetic variation as a predictor of smoking cessation success. A promising preventive and intervention tool for chronic respiratory diseases? Eur Respir J 2009, 33:468-480.
  • [40]Del Ben CM, Vilela JAA, Crippa JAS, Hallak JEC, Labate CM, Zuardi AW: Confiabilidade da “entrevista clinica estruturada para o DSM-IV” – versão clínica traduzida para o português. Rev Bras Psiquiatr 2001, 23(3):156-159.
  • [41]Centers for Disease Control and Prevention (CDC): Cigarette smoking in the United States: current cigarette smoking among U.S. adults aged 18 years and older. 2009. http://www.cdc.gov/tobacco/campaign/tips/resources/data/cigarette-smoking-in-united-states.html
  • [42]Fagerström KO, Schneider NG: Measuring nicotine dependence: a review of the Fagerström Tolerance Questionnaire. J Behav Med 1989, 12:159-182.
  • [43]Carmo JT, Pueyo AA: A adaptação ao português do Fagerström Test for Nicotine Dependence (FTND) para avaliar a dependência e tolerância à nicotina em fumantes. Rev Bras Med 2002, 59(1/2):73-80.
  • [44]Reichert J, Araújo AJ, Gonçalves CMC, Godoy I, Chatkin JM, Sales MPU, Santos SRR SRR: Diretrizes para cessação do tabagismo – 2008. Smoking cessation guidelines – 2008. J Bras Pneumol 2008, 34(10):845-880.
  • [45]Middleton ET, Morice AH: Breath carbon monoxide as an indication of smoking habit. Chest 2000, 117(3):758-763.
  • [46]Ministério da Saúde (Brasil): Secretaria de Atenção à Saúde, Portaria SAS/MS 442/04 de 13 de agosto de 2004. Aprova o Plano de Implantação da Abordagem e Tratamento do Tabagismo no SUS. D.O.U n° 158 17/08/2004. Brasília, DF; Retrieved from: http://dtr2001.saude.gov.br/sas/PORTARIAS/Port2004/PT-442.htm
  • [47]Nunes SOV, Vargas HO, Castro MR, Machado RCB, Carmo DR: Abordagem intensiva. In Abordagem, Prevenção e Tratamento do Tabagismo. Edited by Nunes SOV, Castro MRP. Londrina: Eduel; 2011:97-216.
  • [48]World Health Organization (WHO): The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST): development, reliability and feasibility. Addiction 2002, 97(9):1183-1194.
  • [49]Keskitalo K, Broms U, Heliövaara M, Ripatti S, Surakka I, Perola M, Pitkäniemi J, Peltonen L, Aromaa A, Kaprio J: Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15. Hum Mol Genet 2009, 18:4007-4012.
  • [50]The Tobacco and Genetics Consortium: Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet 2010, 42(5):441-447.
  • [51]Lessov-Schlaggar CN, Pergadia ML, Khroyan TV, Swan GE: Genetics of nicotine dependence and pharmacotherapy. Biochem Pharmacol 2008, 75:178-195.
  • [52]O'Loughlin J, DiFranza J, Tyndale RF, Meshefedjian G, McMillan-Davey E, Clarke PB, Hanley J, Paradis G: Nicotine-dependence symptoms are associated with smoking frequency in adolescents. Am J Prev Med 2003, 25(3):219-225.
  • [53]Hernandez-Lopez S, Garduño J, Mihailescu S: Nicotinic modulation of serotonergic activity in the dorsal raphe nucleus. Rev Neurosci 2013, 24:455-469.
  • [54]Hughes JR: Smoking and suicide: a brief overview. Drug Alcohol Depend 2008, 98:169-178.
  • [55]Ho P-S, Ho KK-J, Huang W-S, Yen C-H, Shih M-C, Shen L-H, Ma K-H, Huang S-Y: Association study of serotonin transporter availability and SLC6A4 gene polymorphisms in patients with major depression. Psychiatry Res 2013, 212:216-222.
  • [56]Maes M, Chang YS, Galecki P, Berk M: A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 2011, 35:676-692.
  • [57]Nunes SOV, Vargas HO, Prado E, Barbosa DS, Melo LP, Moylan S, Dodd S, Berk M: The shared role of oxidative stress and inflammation in major depressive disorder and nicotine dependence. Neurosci Biobehav Rev 2013, 37:1336-1345.
  文献评价指标  
  下载次数:3次 浏览次数:6次