Sexually dimorphic effects of oxytocin receptor gene (OXTR ) variants on Harm Avoidance

Abstract

Background: Recent research has suggested that oxytocin receptor gene (OXTR) variants may account for individual differences in social behavior, the effects of stress and parenting styles. Little is known, however, on a putative role of the gene in heritable temperamental traits.

Methods: We addressed effects of two common OXTR variants, rs237900 and rs237902, on personality dimensions in 99 healthy subjects using the Temperament and Character Inventory.

Results: When sex was controlled for and an OXTR genotype*sex interaction term was included in the regression model, 11% of the variance in Harm Avoidance could be explained (uncorrected p ≤ 0.01). Female carriers of the minor alleles scored highest, and a novel A217T mutation emerged in the most harm avoidant male participant.

Conclusions: Findings lend support to a modulatory effect of common OXTR variants on Harm Avoidance in healthy caucasian women and invite resequencing of the gene in anxiety phenotypes to identify more explanatory functional variation.

Figure 1

Interaction of OXTR genotype ( t =1.26, p =0.20) and sex ( t =−3.05, p =0.003) as predictors of Harm Avoidance mean scores.

Figure 2

Chromatogram (a) and evolutionary conservation plot (b) of a newly identified OXTR mutation, A217T, in a subject scoring on the 98th percentile for Harm Avoidance. Basewise conservation of the amplicon sequence is plotted from 5‘ to 3‘ against the physical position on chromosome 3 using 46 placental mammals featured in the UCSC Genome Browser. A217T maps to a highly conserved region encoding the 5th OXTR transmembrane domain.