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Background  Two important aspects for the development of anxiety disorders are genetic predisposition and alterations in the hypothalamic-pituitary-adrenal (HPA) axis. In order to identify genetic risk-factors for anxiety, the aim of this exploratory study was to investigate possible relationships between genetic polymorphisms in genes important for the regulation and activity of the HPA axis and self-assessed anxiety in healthy individuals.    Methods  DNA from 72 healthy participants, 37 women and 35 men, were included in the analyses. Their DNA was extracted and analysed for the following Single Nucleotide Polymorphisms (SNP)s: rs41423247 in the  NR3C1  gene, rs1360780 in the  FKBP5  gene, rs53576 in the  OXTR  gene, 5-HTTLPR in  SLC6A4  gene and rs6295 in the  HTR1A  gene. Self-assessed anxiety was measured by the State and Trait Anxiety Inventory (STAI) questionnaire.    Results  Self-assessed measure of both STAI-S and STAI-T were significantly higher in female than in male participants ( p  = 0.030 and  p  = 0.036, respectively). For SNP rs41423247 in the  NR3C1  gene, there was a significant difference in females in the score for STAI-S, where carriers of the G allele had higher scores compared to the females that were homozygous for the C allele ( p  < 0.01). For the SNP rs53576 in the  OXTR  gene, there was a significant difference in males, where carriers of the A allele had higher scores in STAI-T compared to the males that were homozygous for the G allele ( p  < 0.01).    Conclusion  This study shows that SNP rs41423247 in the  NR3C1  gene and SNP rs53576 in the  OXTR  gene are associated with self-assessed anxiety in healthy individuals in a gender-specific manner. This suggests that these SNP candidates are possible genetic risk-factors for anxiety.

Genetic risk-factors for anxiety in healthy individuals: polymorphisms in genes important for the HPA axis