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

Stankova T, Eichhammer P, Langguth B, Sand PG - Biol Sex Differ (2012)

Bottom Line: 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.We addressed effects of two common OXTR variants, rs237900 and rs237902, on personality dimensions in 99 healthy subjects using the Temperament and Character Inventory.Female carriers of the minor alleles scored highest, and a novel A217T mutation emerged in the most harm avoidant male participant.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Universitaetsstrasse 84, 93053 Regensburg, Germany. philipp.sand@klinik.uni-regensburg.de.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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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.

Mentions: Detailed examination of the sequence chromatograms revealed one carrier of a novel synonymous variant, Y200Y (TAC > TAT), plus one carrier of a novel missense mutation, A217T (GCT > ACT). The latter coincided with the highest Harm Avoidance score of all male subjects, and the 98th percentile of pooled Harm Avoidance scores under a Gaussian distribution. To obtain more detailed information on the prevalence of this substitution in the general population, we screened an additional set of previously recruited control subjects (healthy by self-report, no TCI data available) originating from the greater Regensburg area using the same experimental protocol (N = 396, 172 men and 224 women). They comprised university students, other hospital employees, and their acquaintances. No further carriers were identified, lowering the total allele frequency to 0.001. A217T maps to a region encoding the fifth OXTR transmembrane domain (TMD), delimited by residues 203 and 225. Evolutionary conservation of this region in mammals is high (Figure 2) and in silico predictions indicated that the variant is possibly damaging (PolyPhen2 score 0.46). Two known OXTR variants, rs4686302, rs61740241, were confirmed in the course of screening the extension sample, plus two novel intronic variants (T > C, chr3: 8,808,677 and G > A, chr3: 8,808,925). Two subjects also carried one novel OXTR missense variant each, E242K (GAG > AAG) and G252A (GGG > GCG) that, however, do not map to any TMD and appear benign (PolyPhen2 score <0.01).


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

Stankova T, Eichhammer P, Langguth B, Sand PG - Biol Sex Differ (2012)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472235&req=5

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.
Mentions: Detailed examination of the sequence chromatograms revealed one carrier of a novel synonymous variant, Y200Y (TAC > TAT), plus one carrier of a novel missense mutation, A217T (GCT > ACT). The latter coincided with the highest Harm Avoidance score of all male subjects, and the 98th percentile of pooled Harm Avoidance scores under a Gaussian distribution. To obtain more detailed information on the prevalence of this substitution in the general population, we screened an additional set of previously recruited control subjects (healthy by self-report, no TCI data available) originating from the greater Regensburg area using the same experimental protocol (N = 396, 172 men and 224 women). They comprised university students, other hospital employees, and their acquaintances. No further carriers were identified, lowering the total allele frequency to 0.001. A217T maps to a region encoding the fifth OXTR transmembrane domain (TMD), delimited by residues 203 and 225. Evolutionary conservation of this region in mammals is high (Figure 2) and in silico predictions indicated that the variant is possibly damaging (PolyPhen2 score 0.46). Two known OXTR variants, rs4686302, rs61740241, were confirmed in the course of screening the extension sample, plus two novel intronic variants (T > C, chr3: 8,808,677 and G > A, chr3: 8,808,925). Two subjects also carried one novel OXTR missense variant each, E242K (GAG > AAG) and G252A (GGG > GCG) that, however, do not map to any TMD and appear benign (PolyPhen2 score <0.01).

Bottom Line: 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.We addressed effects of two common OXTR variants, rs237900 and rs237902, on personality dimensions in 99 healthy subjects using the Temperament and Character Inventory.Female carriers of the minor alleles scored highest, and a novel A217T mutation emerged in the most harm avoidant male participant.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Universitaetsstrasse 84, 93053 Regensburg, Germany. philipp.sand@klinik.uni-regensburg.de.

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.

No MeSH data available.


Related in: MedlinePlus