Studies in families have shown that Panic Disorder (PD) has a familiar pattern: its prevalence is higher in first degree family members than in control groups . Studies involving siblings show that PD concordance is higher in monozygotic than dizygotic twins . These findings propose that genetic factors contribute to the pathogenesis of PD with an estimated heritability of 30–40% , whereas a recent meta-analysis suggests a higher heritability of 48% .
Studies on candidate genes for association have been selected on the basis of the molecular therapeutic drugs and panic-provoking agents . For instance, the response shown by panic patients when treated with Serotonin Selective Reuptake Inhibitors (SSRIs) and the worsening when using a serotoninergic agonist suggest a possible serotoninergic dysfunction in this disorder [2, 6].
The serotoninergic transporter gene (5-HTT) is located in chromosome 17q11.1-q12  and it codes for a membrane protein that reuptakes serotonin from the synaptic cleft. A size repetition polymorphism has been related to functionality of the serotoninergic transporter protein. The polymorphism is a 44 bp insertion or deletion on the promoter gene region (5 – HTTLPR) resulting in two alleles (l-long and s-short). The l allele transcription is two or three times more efficient than the s allele [8, 9]. The s allele is less active, therefore, resulting in lower serotonin reuptake and, consequently, in increased serotonin in the synaptic cleft .
Previous studies found a significant association between s allele and anxiety traits in healthy volunteers . Regarding PD, studies have systematically failed to find any association between this disorder and 5-HTTLPR. This lack of association could be related to the small sample size of studies. However, a recent study has raised the possibility that the l allele could be involved in panic disorder .
Although the controversies between 5-HTTLPR in PD may be related to methodological differences between studies, such as ethnicity, another limitation is lack of statistical power . According to Hirschhorn et al. , out of 166 studies on gene-disease associations, only six replicated previous findings. Possible causes for this inconsistency include studies with small sample sizes [15, 16], as the most realistic genetic association between a polymorphic locus and a disease has been claimed to yield an odds ratio between 1.1 and 1.5 . Thus at least 1000 subjects should be required to detect this association, depending on the prevalence of polymorphism. However, studies typically report sample sizes from 100 to 300 and rarely above 1000 subjects [16, 18], justifying the use of meta-analysis to increase power.
The aim of this study is to attempt to answer whether there is an association between the 5-HTTLPR and PD. As the s allele of 5-HTTLPR is significantly involved in anxiety traits, the assumption is that this polymorphism should be involved in PD.