Se Joo Kim and Chan-Hyung Kim Jewish OCD patients and did not find any signifi- cant association between 5-HT2C receptor poly- morphism and OCD. The 5-HT1Dβ receptor appears to be particu- larly interesting in the pathophysiology of OCD. The 5-HT1Dβ receptor is a terminal autoreceptor involved in the regulation of 5-HT synthesis and release, and is expressed mostly in the limbic region and in the striatum. Gross-Isseroff et al.54 reported that sumatriptan, a selective 5-HT1Dβ agonist, caused significant OCD symptom ex- acerbation. In addition, Stern et al.55 found that the continuous administration of sumatriptan could reduce depression and OC symptoms in three refractory OCD patients. To date, only eight studies of the association between the 5- HT1Dβ gene and OCD have been reported. Two family-based association studies by Mundo et al. 56,57 reported that the G861 allele of the 5-HT1Dβ gene was preferentially transmitted to OCD patients. However, other family-based studies by Camarena et al.,58 Di Bella et al.,59 and Walitza et al.39 did not replicate this result. The other two case-control studies28,60 also did not find any asso- ciation between 5-HT1Dβ G861C polymorphism and OCD. In Korea, we investigated the asso- ciation 5-HT1Dβ G861C and OCD but could not find any significant associations (unpublished). Tryptophan hydroxylase (TPH) gene TPH is the rate-limiting enzyme in the synthesis of 5-HT. Therefore, it has been considered that the variant in TPH may influence serotonin turnover and behaviors controlled by serotonin, such as OCD.61 To date, only three studies of the associa- tion between the TPH1 or 2 genes and OCD have been published. Frisch et al.38 found no asso- ciation between TPH1 and Jewish OCD patients. Walitza et al.39 also did not find transmission disequilibrium for alleles of the SNP rs1800532 (TPH1 gene) in patients with early onset OCD using a TDT test. The TPH2 gene has been re- cently found and received attention because its mRNA was detected exclusively in the brain.62 Mossner et al.63 investigated the association between TPH2, the gene of the novel brain- specific TPH2, in OCD and its role in childhood and adolescent-onset OCD. In analysis of the SNPs, rs4570625 and rs456946 of TPH2, they Yonsei Med J Vol. 47, No. 4, 2006 found a significant preferential transmission of haplotype G-C to OCD. They also found a trend of preferential transmission of the C allele of SNP rs4565946 to the early-onset of OCD. Genes related to dopamine neurotransmission As mentioned above, the most prevailing hypothesis on the mechanism of OCD is the sero- tonin hypothesis. However, about 40% of OCD patients do not respond to SSRIs, and some patients show no convincing functional abnorma- lities related to serotonin.64 Furthermore, the sero- tonin system varies and is interrelated with other neurotransmitters or neuronal circuits.64 Therefore, apart from the main hypothesis suggesting sero- tonin abnormalities, some authors have proposed that dopamine could participate in the pathophy- siology of OCD.65 When high concentrations of dopamine-related drugs, such as amphetamine and bromocriptine, were administered in animal studies, stereotypic behaviors similar to the obses- sive behaviors in OCD patients were observed.65 Administration of dopamine receptor inhibiting drugs in combination with an SSRI reduced obses- sive symptoms in OCD patients who had previ- ously shown resistance to treatment with an SSRI alone.66 Similarly, there have been reports that OC symptoms have emerged during treatment with clozapine, a dopamine receptor D4 (DRD4) antago- nist.67 This evidence obtained from neuroanatomi- cal and pharmacological data suggests that the dopaminergic neurotransmitter system may also be implicated in mediating OCD. Dopamine transporter gene (DAT1) The DAT1 gene is located on chromosome 5p15.3 and has 40 bp variable numbers of tandem repeats (VNTR, with 3 - 11 repeats) on the 3'-un- translated region.68 There is some possibility that these VNTR have an effect on the gene expression and the level of DAT1 protein in the brain.69 However, there have only been a few studies examining the association between DAT1 and OCD. Frisch et al.38 reported that there was no association between the DAT1 gene and OCD in Jews, and Hemmings et al.28 also did not find any difference in the distribution of DAT1 VNTR between the OCD and control groups. In Korea,