Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism

Behavioral and Brain Functions

Tzu-Yun Wang³  Sheng-Yu Lee²  Shiou-Lan Chen²  Yun-Hsuan Chang²  Shih-Heng Chen²  Chun-Hsien Chu²  San-Yuan Huang¹  Nian-Sheng Tzeng¹  Chen-Lin Wang²  I Hui Lee²  Tzung Lieh Yeh²  Yen Kuang Yang²  Ru-Band Lu² 

[1] Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

[2] Department of Psychiatry, National Cheng Kung University Hospital, Tainan, Taiwan

[3] Department of Psychiatry, Tainan Hospital, Department of Health, Executive Yuan, Tainan, Taiwan

关键词: 5-HT1B gene;    Serotonin transporter gene;    Serotonin;    Antisocial alcoholism;   

Others  :  797535
DOI  :  10.1186/1744-9081-8-18

 received in 2011-11-20, accepted in 2012-05-02,  发布年份 2012

【 摘 要 】

Background

Several studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR) and serotonin 1 B receptor (5-HT1B), may be associated with alcoholism, but their results are contradictory because of alcoholism’s heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan.

Methods

We recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD) [antisocial alcoholism (AS-ALC) group (n = 120) and antisocial non-alcoholism (AS-N-ALC) group (n = 153)] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP.

Results

There were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/L_G, and L_G/L_G genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/L_G, and L_G/L_G genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism.

Conclusion

Our study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan’s Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.

【 授权许可】

   
2012 Wang et al; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Cloninger CR: Neurogenetic adaptive mechanisms in alcoholism. Science 1987, 236:410-416.
• [2]Edenberg HJ, Foroud T: The genetics of alcoholism: identifying specific genes through family studies. Addict Biol 2006, 11:386-396.
• [3]Kendler KS, Heath AC, Neale MC, Kessler RC, Eaves LJ: A population-based twin study of alcoholism in women. JAMA 1992, 268:1877-1882.
• [4]Heath AC, Bucholz KK, Madden PA, Dinwiddie SH, Slutske WS, Bierut LJ, Statham DJ, Dunne MP, Whitfield JB, Martin NG: Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychol Med 1997, 27:1381-1396.
• [5]Kendler KS, Prescott CA, Neale MC, Pedersen NL: Temperance board registration for alcohol abuse in a national sample of Swedish male twins, born 1902 to 1949. Arch Gen Psychiatry 1997, 54:178-184.
• [6]Lu RB, Ko HC, Lee JF, Lin WW, Huang SY, Wang TJ, Wu YS, Lu TE, Chou YH: No alcoholism-protection effects of ADH1B*2 allele in antisocial alcoholics among Han Chinese in Taiwan. Alcohol Clin Exp Res 2005, 29:2101-2107.
• [7]Lee SY, Hahn CY, Lee JF, Chen SL, Chen SH, Yeh TL, Kuo PH, Lee IH, Yang YK, Huang SY, et al.: MAOA-uVNTR polymorphism may modify the protective effect of ALDH2 gene against alcohol dependence in antisocial personality disorder. Alcohol Clin Exp Res 2009, 33:985-990.
• [8]Wu CY, Wu YS, Lee JF, Huang SY, Yu L, Ko HC, Lu RB: The association between DRD2/ANKK1, 5-HTTLPR gene, and specific personality trait on antisocial alcoholism among Han Chinese in Taiwan. Am J Med Genet B Neuropsychiatr Genet 2008, 147B:447-453.
• [9]Lee SY, Lin WW, Huang SY, Kuo PH, Wang CL, Wu PL, Chen SL, Wu JY, Ko HC, Lu RB: The relationship between serotonin receptor 1B polymorphisms A-161T and alcohol dependence. Alcohol Clin Exp Res 2009, 33:1589-1595.
• [10]Fils-Aime ML, Eckardt MJ, George DT, Brown GL, Mefford I, Linnoila M: Early-onset alcoholics have lower cerebrospinal fluid 5-hydroxyindoleacetic acid levels than late-onset alcoholics. Arch Gen Psychiatry 1996, 53:211-216.
• [11]Linnoila M, Virkkunen M, Scheinin M, Nuutila A, Rimon R, Goodwin FK: Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sci 1983, 33:2609-2614.
• [12]Linnoila M, De Jong J, Virkkunen M: Family history of alcoholism in violent offenders and impulsive fire setters. Arch Gen Psychiatry 1989, 46:613-616.
• [13]Virkkunen M, Nuutila A, Goodwin FK, Linnoila M: Cerebrospinal fluid monoamine metabolite levels in male arsonists. Arch Gen Psychiatry 1987, 44:241-247.
• [14]Virkkunen M, Rawlings R, Tokola R, Poland RE, Guidotti A, Nemeroff C, Bissette G, Kalogeras K, Karonen SL, Linnoila M: CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. Arch Gen Psychiatry 1994, 51:20-27.
• [15]Kranzler HR, Anton RF: Implications of recent neuropsychopharmacologic research for understanding the etiology and development of alcoholism. J Consult Clin Psychol 1994, 62:1116-1126.
• [16]Sellers EM, Higgins GA, Sobell MB: 5-HT and alcohol abuse. Trends Pharmacol Sci 1992, 13:69-75.
• [17]LeMarquand D, Pihl RO, Benkelfat C: Serotonin and alcohol intake, abuse, and dependence: findings of animal studies. Biol Psychiatry 1994, 36:395-421.
• [18]Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL: Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996, 274:1527-1531.
• [19]Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP: Allelic variation of human serotonin transporter gene expression. J Neurochem 1996, 66:2621-2624.
• [20]Heinz A, Jones DW, Mazzanti C, Goldman D, Ragan P, Hommer D, Linnoila M, Weinberger DR: A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity. Biol Psychiatry 2000, 47:643-649.
• [21]Little KY, McLaughlin DP, Zhang L, Livermore CS, Dalack GW, McFinton PR, DelProposto ZS, Hill E, Cassin BJ, Watson SJ, Cook EH: Cocaine, ethanol, and genotype effects on human midbrain serotonin transporter binding sites and mRNA levels. Am J Psychiatry 1998, 155:207-213.
• [22]McHugh RK, Hofmann SG, Asnaani A, Sawyer AT, Otto MW: The serotonin transporter gene and risk for alcohol dependence: a meta-analytic review. Drug Alcohol Depend 108:1-6.
• [23]Feinn R, Nellissery M, Kranzler HR: Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 2005, 133B:79-84.
• [24]Parsian A, Cloninger CR: Serotonergic pathway genes and subtypes of alcoholism: association studies. Psychiatr Genet 2001, 11:89-94.
• [25]Hallikainen T, Saito T, Lachman HM, Volavka J, Pohjalainen T, Ryynanen OP, Kauhanen J, Syvalahti E, Hietala J, Tiihonen J: Association between low activity serotonin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior. Mol Psychiatry 1999, 4:385-388.
• [26]Sander T, Harms H, Dufeu P, Kuhn S, Hoehe M, Lesch KP, Rommelspacher H, Schmidt LG: Serotonin transporter gene variants in alcohol-dependent subjects with dissocial personality disorder. Biol Psychiatry 1998, 43:908-912.
• [27]Ishiguro H, Saito T, Akazawa S, Mitushio H, Tada K, Enomoto M, Mifune H, Toru M, Shibuya H, Arinami T: Association between drinking-related antisocial behavior and a polymorphism in the serotonin transporter gene in a Japanese population. Alcohol Clin Exp Res 1999, 23:1281-1284.
• [28]Schuckit MA, Mazzanti C, Smith TL, Ahmed U, Radel M, Iwata N, Goldman D: Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABA alpha 6 receptors and the serotonin transporter in the level of response to alcohol: a pilot study. Biol Psychiatry 1999, 45:647-651.
• [29]Nakamura M, Ueno S, Sano A, Tanabe H: The human serotonin transporter gene linked polymorphism (5-HTTLPR) shows ten novel allelic variants. Mol Psychiatry 2000, 5:32-38.
• [30]Hu X, Oroszi G, Chun J, Smith TL, Goldman D, Schuckit MA: An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk. Alcohol Clin Exp Res 2005, 29:8-16.
• [31]Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, et al.: Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 2006, 78:815-826.
• [32]Delbruck SJ, Wendel B, Grunewald I, Sander T, Morris-Rosendahl D, Crocq MA, Berrettini WH, Hoehe MR: A novel allelic variant of the human serotonin transporter gene regulatory polymorphism. Cytogenet Cell Genet 1997, 79:214-220.
• [33]Gelernter J, Kranzler H, Cubells JF: Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects. Hum Genet 1997, 101:243-246.
• [34]Kunugi H, Hattori M, Kato T, Tatsumi M, Sakai T, Sasaki T, Hirose T, Nanko S: Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder. Mol Psychiatry 1997, 2:457-462.
• [35]Narita N, Narita M, Takashima S, Nakayama M, Nagai T, Okado N: Serotonin transporter gene variation is a risk factor for sudden infant death syndrome in the Japanese population. Pediatrics 2001, 107:690-692.
• [36]Barnes NM, Sharp T: A review of central 5-HT receptors and their function. Neuropharmacology 1999, 38:1083-1152.
• [37]Crabbe JC, Belknap JK, Buck KJ: Genetic animal models of alcohol and drug abuse. Science 1994, 264:1715-1723.
• [38]Saudou F, Amara DA, Dierich A, LeMeur M, Ramboz S, Segu L, Buhot MC, Hen R: Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science 1994, 265:1875-1878.
• [39]Crabbe JC, Phillips TJ, Feller DJ, Hen R, Wenger CD, Lessov CN, Schafer GL: Elevated alcohol consumption in null mutant mice lacking 5-HT1B serotonin receptors. Nat Genet 1996, 14:98-101.
• [40]Cigler T, LaForge KS, McHugh PF, Kapadia SU, Leal SM, Kreek MJ: Novel and previously reported single-nucleotide polymorphisms in the human 5-HT(1B) receptor gene: no association with cocaine or alcohol abuse or dependence. Am J Med Genet 2001, 105:489-497.
• [41]Fehr C, Grintschuk N, Szegedi A, Anghelescu I, Klawe C, Singer P, Hiemke C, Dahmen N: The HTR1B 861 G>C receptor polymorphism among patients suffering from alcoholism, major depression, anxiety disorders and narcolepsy. Psychiatry Res 2000, 97:1-10.
• [42]Lappalainen J, Long JC, Eggert M, Ozaki N, Robin RW, Brown GL, Naukkarinen H, Virkkunen M, Linnoila M, Goldman D: Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations. Arch Gen Psychiatry 1998, 55:989-994.
• [43]Huang YY, Oquendo MA, Friedman JM, Greenhill LL, Brodsky B, Malone KM, Khait V, Mann JJ: Substance abuse disorder and major depression are associated with the human 5-HT1B receptor gene (HTR1B) G861C polymorphism. Neuropsychopharmacology 2003, 28:163-169.
• [44]Underwood MD, Mann JJ, Arango V: Serotonergic and noradrenergic neurobiology of alcoholic suicide. Alcohol Clin Exp Res 2004, 28:57S-69S.
• [45]Huang YY, Grailhe R, Arango V, Hen R, Mann JJ: Relationship of psychopathology to the human serotonin1B genotype and receptor binding kinetics in postmortem brain tissue. Neuropsychopharmacology 1999, 21:238-246.
• [46]Kranzler H, Lappalainen J, Nellissery M, Gelernter J: Association study of alcoholism subtypes with a functional promoter polymorphism in the serotonin transporter protein gene. Alcohol Clin Exp Res 2002, 26:1330-1335.
• [47]Gorwood P, Aissi F, Batel P, Ades J, Cohen-Salmon C, Hamon M, Boni C, Lanfumey L: Reappraisal of the serotonin 5-HT(1B) receptor gene in alcoholism: of mice and men. Brain Res Bull 2002, 57:103-107.
• [48]Goldstein RB, Dawson DA, Saha TD, Ruan WJ, Compton WM, Grant BF: Antisocial behavioral syndromes and DSM-IV alcohol use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Alcohol Clin Exp Res 2007, 31:814-828.
• [49]Ross HE, Glaser FB, Germanson T: The prevalence of psychiatric disorders in patients with alcohol and other drug problems. Arch Gen Psychiatry 1988, 45:1023-1031.
• [50]Hesselbrock VM, Hesselbrock MN, Stabenau JR: Alcoholism in men patients subtyped by family history and antisocial personality. J Stud Alcohol 1985, 46:59-64.
• [51]van den Bree MB, Svikis DS, Pickens RW: Genetic influences in antisocial personality and drug use disorders. Drug Alcohol Depend 1998, 49:177-187.
• [52]Hwu HG, Yeh EK, Chang LY: Prevalence of psychiatric disorders in Taiwan defined by the Chinese Diagnostic Interview Schedule. Acta Psychiatr Scand 1989, 79:136-147.
• [53]Endicott J, Spitzer RL: A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 1978, 35:837-844.
• [54]Huang SY, Lin WW, Ko HC, Lee JF, Wang TJ, Chou YH, Yin SJ, Lu RB: Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence. Alcohol Clin Exp Res 2004, 28:374-384.
• [55]Goodwin RD, Hamilton SP: Lifetime comorbidity of antisocial personality disorder and anxiety disorders among adults in the community. Psychiatry Res 2003, 117:159-166.
• [56]Hesselbrock V, Stabenau J, Hesselbrock M, Mirkin P, Meyer R: A comparison of two interview schedules. The schedule for affective disorders and Schizophrenia-Lifetime and the National Institute for Mental Health Diagnostic Interview Schedule. Arch Gen Psychiatry 1982, 39:674-677.
• [57]Rogers R, Cunnien AJ: Multiple schedule of affective disorders and schizophrenia (SADS) in the assessment of criminal defendants. J Forensic Sci 1986, 31:222-230.
• [58]Maron E, Tammiste A, Kallassalu K, Eller T, Vasar V, Nutt DJ, Metspalu A: Serotonin transporter promoter region polymorphisms do not influence treatment response to escitalopram in patients with major depression. Eur Neuropsychopharmacol 2009, 19:451-456.
• [59]Wendland JR, Martin BJ, Kruse MR, Lesch KP, Murphy DL: Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Mol Psychiatry 2006, 11:224-226.
• [60]Bowirrat A, Oscar-Berman M: Relationship between dopaminergic neurotransmission, alcoholism, and Reward Deficiency syndrome. Am J Med Genet B Neuropsychiatr Genet 2005, 132B:29-37.
• [61]Faul F, Erdfelder E, Buchner A, Lang AG: Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009, 41:1149-1160.
• [62]Faul F, Erdfelder E, Lang AG, Buchner A: G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007, 39:175-191.
• [63]Lyons-Ruth K, Holmes BM, Sasvari-Szekely M, Ronai Z, Nemoda Z, Pauls D: Serotonin transporter polymorphism and borderline or antisocial traits among low-income young adults. Psychiatr Genet 2007, 17:339-343.
• [64]Reif A, Rosler M, Freitag CM, Schneider M, Eujen A, Kissling C, Wenzler D, Jacob CP, Retz-Junginger P, Thome J, et al.: Nature and nurture predispose to violent behavior: serotonergic genes and adverse childhood environment. Neuropsychopharmacology 2007, 32:2375-2383.
• [65]Sadeh N, Javdani S, Jackson JJ, Reynolds EK, Potenza MN, Gelernter J, Lejuez CW, Verona E: Serotonin transporter gene associations with psychopathic traits in youth vary as a function of socioeconomic resources. J Abnorm Psychol 2010, 119:604-609.
• [66]Lu RB, Lee JF, Huang SY, Lee SY, Chang YH, Kuo PH, Chen SL, Chen SH, Chu CH, Lin WW, et al.: Interaction between ALDH2*1*1 and DRD2/ANKK1 TaqI A1A1 genes may be associated with antisocial personality disorder not co-morbid with alcoholism. Addict Biol
• [67]Baumgarten HG, Grozdanovic Z: Psychopharmacology of central serotonergic systems. Pharmacopsychiatry 1995, 28(Suppl 2):73-79.
• [68]Parsons LH, Weiss F, Koob GF: Serotonin1b receptor stimulation enhances dopamine-mediated reinforcement. Psychopharmacology (Berl) 1996, 128:150-160.
• [69]Walsh SL, Cunningham KA: Serotonergic mechanisms involved in the discriminative stimulus, reinforcing and subjective effects of cocaine. Psychopharmacology (Berl) 1997, 130:41-58.
• [70]Hallbus M, Magnusson T, Magnusson O: Influence of 5-HT1B/1D receptors on dopamine release in the guinea pig nucleus accumbens: a microdialysis study. Neurosci Lett 1997, 225:57-60.
• [71]Yadid G, Pacak K, Kopin IJ, Goldstein DS: Endogenous serotonin stimulates striatal dopamine release in conscious rats. J Pharmacol Exp Ther 1994, 270:1158-1165.
• [72]Cesura AM, Pletscher A: The new generation of monoamine oxidase inhibitors. Prog Drug Res 1992, 38:171-297.
• [73]Keung WM, Vallee BL: Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase. Proc Natl Acad Sci U S A 1993, 90:1247-1251.
• [74]Wang TJ, Huang SY, Lin WW, Lo HY, Wu PL, Wang YS, Wu YS, Ko HC, Shih JC, Lu RB: Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan. Prog Neuropsychopharmacol Biol Psychiatry 2007, 31:108-114.
• [75]Goldman N, Glei DA, Lin YH, Weinstein M: The serotonin transporter polymorphism (5-HTTLPR): allelic variation and links with depressive symptoms. Depress Anxiety 2010, 27:260-269.