title: Rare genotype combination of the serotonin transporter gene associated with treatment response in severe personality disorder.
abstract: The insertion deletion (ins/del) polymorphism of the serotonin transporter gene (5-HTTLPR) has been associated with several psychiatric phenotypes and antidepressant's response. We investigated, in a large cohort of 5,608 controls and subjects suffering from various psychiatric disorders, the frequency of haplotypes and corresponding genotypes combining the 5-HTTLPR and the other serotonin transporter promoter functional variant (rs25531). We showed that rs25531 lies 18 bp 5' to the site where the 43 bp (and not 44 bp as previously described) ins/del defines the 14- and 16-repeat alleles. These polymorphisms should therefore be considered as four alleles instead of a triallelic unique locus. The very rare G-14/G-16 genotype was carried on by only three subjects. These are women with a history of suicide attempt with a psychiatric history strongly suggesting a borderline personality disorder. Two of them have shown a non-response to serotoninergic antidepressant. Interestingly, in one of them was observed a spectacular response after the introduction of bupropion. The genotyping droved our therapeutic approach, by preferring a dopaminergic over a serotoninergic agent. This study highlights the usefulness of studying very rare clinical cases as well as rare variants, in order to deal with the biological heterogeneity of spectral disorders. © 2010 Wiley-Liss, Inc.
authors.affiliation: Department of Psychiatry, University of Geneva, Geneva, Switzerland.
authors.forename: Nader
authors.initials: N
authors.lastname: Perroud
authors.forename: Annick
authors.initials: A
authors.lastname: Salzmann
authors.forename: Pilar A
authors.initials: PA
authors.lastname: Saiz
authors.forename: Enrique
authors.initials: E
authors.lastname: Baca-Garcia
authors.forename: Marco
authors.initials: M
authors.lastname: Sarchiapone
authors.forename: Maria P
authors.initials: MP
authors.lastname: Garcia-Portilla
authors.forename: Vladimir
authors.initials: V
authors.lastname: Carli
authors.forename: Concepción
authors.initials: C
authors.lastname: Vaquero-Lorenzo
authors.forename: Isabelle
authors.initials: I
authors.lastname: Jaussent
authors.forename: Dominique
authors.initials: D
authors.lastname: Mouthon
authors.forename: Monique
authors.initials: M
authors.lastname: Vessaz
authors.forename: Philippe
authors.initials: P
authors.lastname: Huguelet
authors.forename: Philippe
authors.initials: P
authors.lastname: Courtet
authors.forename: Alain
authors.initials: A
authors.lastname: Malafosse
mesh_terms: D000328:Adult; D000483:Alleles; D000928:Antidepressive Agents / Q000627:therapeutic use; D001883:Borderline Personality Disorder / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human