title: Gender-specific association between serotonin transporter polymorphisms (5-HTTLPR and rs25531) and neuroticism, anxiety and depression in well-defined healthy Han Chinese.
abstract: A tri-allelic serotonin transporter promoter polymorphism (5-HTTLPR/rs25531) more effectively determines the levels of transcriptional efficacy than that with the bi-allelic 5-HTTLPR polymorphism in vitro. Both are reportedly associated with personality traits of negative emotionality, but with conflicting findings. One explanation for this is that a gender difference may play a role in genetic contribution. Here, we hypothesized that the tri-allelic genotype of the serotonin transporter is more closely linked to neuroticism, an anxiety- and depression-related trait, than the bi-allelic variation, particularly in a gender-dependent way.
  
  
  
  The genotypes of the 5-HTTLPR and rs25531 loci were determined in 1139 well-defined physically and mentally healthy Han Chinese (550 men, 589 women; mean age 38.3±10.3 years). All participants completed the neuroticism measure of the short-form Maudsley Personality Inventory (MPI). The levels of anxiety and depression were assessed by the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI), respectively.
  
  
  
  A significant tri-allelic genotype-by-gender interaction effect was found in the MPI-neuroticism measure. S'S' homozygotes were associated with higher neuroticism than L' allele carriers in men. Also, both the BAI and BDI scores were higher in the S'S' homozygotic men. In the bi-allelic analyses, however, there was only an association between SS genotype and MPI-neuroticism in men.
  
  
  
  Sub-analyses by gender-stratification may reduce the statistical power.
  
  
  
  Our findings confirm that gender differences exist in the genetic contributions of the serotonin transporter in human neuroticism, and anxiety/depression. Our data provide further support for rs25531, strengthening the effects of 5-HTTLPR.
authors: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors: Chuan-Chia
authors: CC
authors: Chang
authors: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Hsin-An
authors: HA
authors: Chang
authors: Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Wen-Hui
authors: WH
authors: Fang
authors: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Tieh-Ching
authors: TC
authors: Chang
authors: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. Electronic address: hsy@ndmctsgh.edu.tw.
authors: San-Yuan
authors: SY
authors: Huang
mesh_terms: D000328:Adult; D000483:Alleles; D001007:Anxiety / Q000235:genetics; D001008:Anxiety Disorders / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002681:China; D003863:Depression / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075384:Neuroticism; D010551:Personality / Q000235:genetics; D010555:Personality Inventory; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: Anxiety; Depression; Gender differences; Neuroticism; Serotonin transporter; Tri-allelic 5-HTTLPR polymorphism