Serotonin transporter gene polymorphism in eating disorders: Data from a new biobank and META-analysis of previous studies

Objectives Growing interest focuses on the association between 5-HTTLPR polymorphism and eating disorders (ED), but published findings have been conflicting. Methods The Italian BIO.VE.D.A. biobank provided 976 samples (735 ED patients and 241 controls) for genotyping. We conducted a literature search of studies published up to 1 April 2015, including studies reporting on 5HTTLPR genotype and allele frequencies in obesity and/or ED. We ran a meta-analysis, including data from BIO.VE.D.A. – comparing low and high-functioning genotype and allele frequencies in ED vs. controls. Results Data from 21 studies, plus BIO.VE.D.A., were extracted providing information from 3,736 patients and 2,707 controls. Neither low- nor high-functioning genotype frequencies in ED patients, with both bi- and tri-allelic models, differed from controls. Furthermore, neither low- nor high-functioning allele frequencies in ED or in BN, in both bi- and triallelic models, differed from control groups. After sensitivity analysis, results were the same in AN vs. controls. Results remained unaltered when investigating recessive and dominant models. Conclusions 5HTTLPR does not seem to be associated with ED in general, or with AN or BN in particular. Future studies in ED should explore the role of ethnicity and psychiatric comorbidity as a possible source of bias.

[1]  Shin-ya Watanabe,et al.  Polymorphism in the promoter of the gene for the serotonin transporter affects the age of onset of major depressive disorder in the Japanese population. , 2015, Journal of affective disorders.

[2]  M. Weissman,et al.  Genetic variants within the serotonin transporter associated with familial risk for major depression , 2015, Psychiatry Research.

[3]  L. Petersen,et al.  The incidence of eating disorders in a Danish register study: Associations with suicide risk and mortality. , 2015, Journal of psychiatric research.

[4]  A. García-Blanco,et al.  Prevalence and comorbidity of eating disorders among a community sample of adolescents: 2-year follow-up , 2015, Psychiatry Research.

[5]  S. Shoib,et al.  5-Hydroxy tryptamine transporter (5HTT) gene promoter region polymorphism in anxiety and depressive disorders , 2014, Medical journal of the Islamic Republic of Iran.

[6]  I. Ntalla,et al.  A genome-wide association study of anorexia nervosa , 2011, Molecular Psychiatry.

[7]  H. Oflaz,et al.  Assessment of myocardial damage by cardiac MRI in patients with anorexia nervosa. , 2013, The International journal of eating disorders.

[8]  D. Mrazek,et al.  "Diminished" association between the serotonin transporter linked polymorphism (5HTTLPR) and body mass index in a large psychiatric sample. , 2013, Journal of Affective Disorders.

[9]  H. Steiger,et al.  Epistatic interaction between 5HTTLPR and TPH2 polymorphisms predicts novelty seeking in women with bulimia nervosa spectrum disorders , 2013, Psychiatry Research.

[10]  C. Faravelli,et al.  Association between serotonin transporter gene polymorphism and eating disorders outcome: A 6‐year follow‐up study , 2012, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[11]  Janet Treasure,et al.  World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Eating Disorders , 2011, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[12]  A. Ziegler,et al.  Investigating Hardy–Weinberg equilibrium in case–control or cohort studies or meta-analysis , 2011, Breast Cancer Research and Treatment.

[13]  Ingo W. Nader,et al.  Gene–environment interaction in anorexia nervosa: relevance of non-shared environment and the serotonin transporter gene , 2011, Molecular Psychiatry.

[14]  A. Serretti,et al.  The 5-HTTLPR polymorphism and eating disorders: a meta-analysis. , 2011, The International journal of eating disorders.

[15]  H. Steiger,et al.  Molecular-genetic correlates of self-harming behaviors in eating-disordered women: Findings from a combined Canadian–German sample , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[16]  Pao-Yen Lin,et al.  Association between serotonin transporter gene polymorphism and eating disorders: a meta-analytic study. , 2010, The International journal of eating disorders.

[17]  S. Ehrlich,et al.  The 5-HTTLPR polymorphism, platelet serotonin transporter activity and platelet serotonin content in underweight and weight-recovered females with anorexia nervosa , 2010, European Archives of Psychiatry and Clinical Neuroscience.

[18]  H. Steiger,et al.  Association of trait-defined, eating-disorder sub-phenotypes with (biallelic and triallelic) 5HTTLPR variations. , 2009, Journal of psychiatric research.

[19]  H. Steiger,et al.  Serotonin-system polymorphisms (5-HTTLPR and -1438G/A) and responses of patients with bulimic syndromes to multimodal treatments. , 2008, The Journal of clinical psychiatry.

[20]  H. Steiger,et al.  Relevance of the 5-HTTLPR polymorphism and childhood abuse to increased psychiatric comorbidity in women with bulimia-spectrum disorders. , 2008, The Journal of clinical psychiatry.

[21]  H. Steiger,et al.  Dissocial behavior, the 5HTTLPR polymorphism, and maltreatment in women with bulimic syndromes , 2008, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[22]  S. Pocock,et al.  Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies , 2007, BMJ : British Medical Journal.

[23]  J. Kornhuber,et al.  Association of catecholamine-O-methyltransferase and 5-HTTLPR genotype with eating disorder-related behavior and attitudes in females with eating disorders , 2006, Psychiatric genetics.

[24]  David Goldman,et al.  Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression. , 2006, The American journal of psychiatry.

[25]  S. Easteal,et al.  Serotonin transporter polymorphisms and clinical response to sertraline across ethnicities , 2006, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[26]  David Goldman,et al.  Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. , 2006, American journal of human genetics.

[27]  J. Hauser,et al.  The 5-HT2A –1438 A/G and 5-HTTLPR Polymorphisms and Personality Dimensions in Adolescent Anorexia Nervosa: Association Study , 2006, Neuropsychobiology.

[28]  M. Maj,et al.  Association of a functional serotonin transporter gene polymorphism with binge eating disorder , 2006, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[29]  M. Maj,et al.  Investigation of the Serotonin Transporter Regulatory Region Polymorphism in Bulimia Nervosa: Relationships to Harm Avoidance, Nutritional Parameters, and Psychiatric Comorbidity , 2006, Psychosomatic medicine.

[30]  K. Nunn,et al.  Epistatic interaction between the monoamine oxidase A and serotonin transporter genes in anorexia nervosa , 2005, European Journal of Human Genetics.

[31]  H. Steiger,et al.  Personality subtyping and bulimia nervosa: psychopathological and genetic correlates , 2005, Psychological Medicine.

[32]  S. Higuchi,et al.  Serotonin transporter regulatory region polymorphism is associated with anorexia nervosa , 2004, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[33]  G. Tsai,et al.  Association between serotonin transporter gene promoter polymorphism and suicide: results of a meta-analysis , 2004, Biological Psychiatry.

[34]  M. Delgado,et al.  Polymorphisms within the promoter and the intron 2 of the serotonin transporter gene in a population of bulimic patients , 2003, Neuroscience Letters.

[35]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[36]  J. Boulenger,et al.  Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene , 2001, Molecular Psychiatry.

[37]  M. Cavallini,et al.  Serotonin transporter linked polymorphic region in anorexia nervosa and bulimia nervosa , 2000, Molecular Psychiatry.

[38]  A. Markham,et al.  Analysis of the serotonin transporter gene linked polymorphism (5-HTTLPR) in anorexia nervosa. , 2000, American journal of medical genetics.

[39]  F. Poustka,et al.  Serotonin transporter gene-linked polymorphic region: allele distributions in relationship to body weight and in anorexia nervosa. , 1997, Life sciences.

[40]  K. Lesch,et al.  Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region , 1996, Science.

[41]  P Riederer,et al.  Allelic Variation of Human Serotonin Transporter Gene Expression , 1996, Journal of neurochemistry.

[42]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[43]  M. Carter Diagnostic and Statistical Manual of Mental Disorders, 5th ed. , 2014 .

[44]  Sharon C. Lyter,et al.  Diagnostic and Statistical Manual of Mental Disorders: Making it Work for Social Work , 2012 .

[45]  L. Šlachtová,et al.  Polymorphisms in serotonin-related genes in anorexia nervosa. The first study in Czech population and metaanalyses with previously performed studies. , 2009, Folia biologica.

[46]  Xavier Estivill,et al.  Contribution of the serotoninergic system to anxious and depressive traits that may be partially responsible for the phenotypical variability of bulimia nervosa. , 2008, Journal of psychiatric research.

[47]  M. Maj,et al.  Self-injurious behavior and attempted suicide in purging bulimia nervosa: associations with psychiatric comorbidity. , 2008, Journal of affective disorders.

[48]  P. Gorwood Eating Disorders, Serotonin Transporter Polymorphisms and Potential Treatment Response , 2004, American journal of pharmacogenomics : genomics-related research in drug development and clinical practice.

[49]  G. Siest,et al.  Association of a functional 5-HT transporter gene polymorphism with anorexia nervosa and food intake , 2001, Molecular Psychiatry.