Gender-specific association between serotonin transporter polymorphisms (5-HTTLPR and rs25531) and neuroticism, anxiety and depression in well-defined healthy Han Chinese

Background: 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. Methods: 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. Results: 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. Limitations: Sub-analyses by gender-stratification may reduce the statistical power. Conclusions: Our findings confirm that gender differences exist in the genetic contributions of the serotonim transporter in human neuroticism, and anxiety/depression. Our data provide further support for rs25531 strengthening the effects of 5-HTTLPR.