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Interaction of serotonergic and noradrenergic gene variants in panic disorder

Objective Panic disorder is an anxiety disorder with an estimated heritability of 48%. Associations findings have been obtained with candidate genes from both serotonergic and noradrenergic pathways including regulatory and coding variants of the serotonin receptor 1A gene, the monoamine oxidase A gene, the catechol-O-methyltransferase gene and the norepinephrine transporter gene. Methods In the present study, an analysis of interactions between the functional serotonin receptor 1A polymorphism, the norepinephrine transporter variants and the other respective polymorphisms of the above-mentioned genes is reported. The analysis is based on genotype results from 115 cases and 115 age and sex-matched controls. Results A nominally significant (P=0.04) interaction between the serotonin receptor 1A and the catechol-O-methyltransferase polymorphisms was observed. Stratified analysis revealed that the odds ratio of each polymorphism was highest in the presence of the low-risk genotype(s) of the other polymorphism and low in the presence of the high-risk genotype(s) of the other polymorphism. Conclusions This is the first possible interaction of genetic variations in panic disorder that has been observed. As the sample size was small and no adjustment for multiple testing was made, the assessment of the interacting risk alleles needs replication in a larger sample with higher power.