Novel 5 '-regulatory region polymorphisms of the 5-HT2C receptor gene: association study with panic disorder

Candidate genes for association studies in panic disorder are often selecte d on the basis of molecular mechanisms of drugs utilized in challenge tests such as m-chlorophenylpiperazine (mCPP), a non-selective 5-HT2C receptor a gonist. Two novel, adjacent polymorphisms [(GT)12-18 and (CT)4-5] in the 5' -regulatory region of the X-chromosomal 5-HT2C receptor gene have recently been reported. We determined the allele frequency of long vs. short polymor phism haplotypes in a German and an Italian sample (combined n = 211) of pa nic disorder patients (DSM-III-R) and compared it with allele frequencies i n two ethnically matched control samples (combined n = 226). In the German sample, a comparison of female genotypes containing the short haplotype vs. female genotypes containing only long haplotypes showed a significant diff erence (p = 0.01, chi (2) analysis). In the Italian sample, however, this o bservation could not be replicated (p = 0.54, chi (2) analysis). This argue s against a major role for these promoter-associated 5-MT,, receptor gene l ength polymorphisms in the aetiopathogenesis of panic disorder.