Genetics of Obsessive-Compulsive Disorder we investigated the differences of genotype distri- butions of the DAT1 gene between 115 OCD patients and 160 normal controls.70 Because a previous study showed that the 10-repeats allele is reported to increase DAT1 gene expression compared with the 7-, 9-, and 11-repeats alleles,71 we classified the genotype of DAT1 into 10/10- repeats and non-10/10-repeats groups. However, we did not find any significant association between the DAT1 gene and OCD. Also, there were no sig- nificant differences in total Y-BOCS scores, global assessment of functioning scores, and total Hamil- ton depression rating scale scores between the patients with 10/10-repeats and non-10/10- repeats genotypes in OCD patients. Considering our results, in consideration with the combined results of the two previous studies, suggest that DAT1 gene polymorphism is not likely to confer susceptibility to OCD. Dopamine receptor genes Because of the phenomena of emerging OC symptoms after treatment with clozapine, the DRD4 gene has been the focus of genetic studies of OCD. The DRD4 gene was characterized by the insertion of 2 - 10 of 48 bp imperfect tandem repeats in the encoding region of the third exon.72 Billet et al.73 genotyped more than 118 Canadian OCD patients for DAT1 (40 bp VNTR), DRD2 (TaqIA), DRD3 (MscI), and DRD4 (48 bp VNTR). They found significant differences in allele fre- quencies between patients and controls only for the DRD4 gene. However, Frisch et al.38 reported that there were no significant differences of geno- type distributions of DRD4 between OCD and control patients. Hemmings et al.28 also reported negative results in an Afrikaner population. Meanwhile, Millet et al.74 found different results from both a French family-based and population- based association studies. In their study, an ex- tended transmission-disequilibrium test for pre- ferential allele transmission in OCD showed an absence of transmission of 2-repeats allele of DRD4 gene (48 bp VNTR). In a population-based association study, they found a significantly lower frequency of 2-repeats allele in OCD than in con- trols. Recently, a study showed a significantly lower frequency of the DRD4 VNTR 7-repeat allele of early onset OCD than that of late-onset OCD in South African Caucasians, but not in Afrikaners.75 In Korea, we classified the DRD4 genes (48 bp VNTR) of 115 OCD patients to the short genotype (genotype with at least one copy of the 2-repeats) and long genotype (genotype without a 2-repeats). We could determine that the short genotype frequency of DRD4 was significantly higher in OCD patients than in normal control groups.76 However, contrary to a previous study by Hem- mings et al.,75 we found no difference in genotype frequencies between the early-onset OCD (age of onset < 17) group and the late-onset OCD (age of onset 17) group.76 In conclusion, there are still inconsistent results of the association between the DRD4 gene and OCD, but some studies74 (in- cluding ours76) suggest the possibility that the 2-repeats allele or a nearby genetic variation could have a protective effect against OCD symptoms. There have only been a few studies on the DRD2 gene in OCD. Nicollini et al.51 performed an association analysis of the DRD2 and DRD3 gene in 67 OCD patients and 54 controls. Although they did not observe any significant associations between these genes and OCD, they found a higher frequency of A2/A2 of DRD2 in OCD patients with tics (N = 12). As mentioned above, Billet et al.73 also did not find a significant asso- ciation between DRD2 and OCD. Most recently, Denys et al.77 examined 150 OCD patients (56 males) and 150 controls (79 males). They could not find any significant differences in genotype distri- bution of DRD2 between the two groups. However, when they stratified the sample by gender, they found higher frequency of the DRD2 A2 allele in male OCD patients compared to male controls. However, their sample size of male OCD patients seemed too small to draw a definite con- clusion, and further analysis of larger samples is warranted to confirm their data. To date, there have been only three studies con- cerning the associations between the DRD3 gene and OCD. All of these studies showed no asso- ciation between the Ser9Gly variant of DRD3 gene and OCD.51,73,78 Genes related to the metabolism of neurotr- ansmitters Catechol-O-methyltransferase (COMT) is an en- Yonsei Med J Vol. 47, No. 4, 2006