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

- The SS genotype of the bi-allelic 5-HTTLPR was associated with neuroticism in men.
- When combining the rs25531 (tri-allelic approach), the association became stronger.
- Men with the tri-allelic S′S′ genotype also had higher anxiety/depression scores.
- Women showed a non-significant pattern across both the 5-HTTLPR classifications.
- Our data provide further support for rs25531 strengthening the effects of 5-HTTLPR.

BackgroundA 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.MethodsThe 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.ResultsA 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.LimitationsSub-analyses by gender-stratification may reduce the statistical power.ConclusionsOur 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.