Se Joo Kim and Chan-Hyung Kim zyme involved in the inactivation of catechol- amines, including adrenaline, noradrenaline, and dopamine. A polymorphism in the human COMT gene (G472A) results in a valine (Val) to methi- onine (Met) amino acid substitution (Val158Met) and also reduces the activity of the enzyme to one quarter of that encoded by the Val allele.79 The alleles are codominant, and heterozygotic patients (Val/Met genotype) have intermediate levels of COMT activity in comparison to homo- zygous individuals.80 There have been several studies about the possible role of the COMT gene in OCD. Karayiorgou and colleagues per- formed population-based81 and family-based association82 studies and reported that in both studies the low activity allele (Met158) is signifi- cantly associated with susceptibility to OCD in males only. Contrary to these results, Schindler et al.83 used a family-based population analysis and demonstrated a tendency for an association between homozygosity (Met/Met or Val/Val) at the COMT locus and OCD. Alsobrook et al. col- lected 56 OCD probands and their parents, and reported a mildly significant association with the low-activity COMT allele in female probands of OCD, but not in male probands. Their findings of gender dimorphism contradict previous results by Karayiorgou and colleagues.81,82 Meanwhile, some researchers have reported that the hetero- zygous genotype (Val/Met) was significantly more common than expected in the Afrikaner OCD population.84 However, other researchers could not find any significant associations between the COMT gene and OCD.49,85,86 In Korea, we analyzed the genotype of COMT in 124 OCD patients and 170 normal controls, but we did not find any differences of genotype distribution between the two groups (unpublished). MAOA is another important enzyme that de- grades biogenic amines (noradrenaline, serotonin, and, to a lesser degree, dopamine). There are two polymorphisms which are related to the level of enzymatic activity.87 The first polymorphism, which is located 1.2 kb upstream of the MAOA coding sequences, consists of a 30 bp repeated sequence present in 2-, 3-, 3.5-, 4-, or 5-repeats, and it has been designated MAOA-uVNTR. This polymorphism is functional, in that 3.5-, 4- and 5- repeats are transcribed 2-3 times more efficiently Yonsei Med J Vol. 47, No. 4, 2006 than those with 3- and 2-repeats.88 The second polymorphism is a T to C substitution on exon 14 (EcoRV), and the T allele is related to lower enzyme activity.87 Camarena et al.89 examined the MAO-A/EcoRV polymorphism in a sample of 122 OCD patients and 124 healthy subjects and found that the T allele was associated with OCD in female patients by family-based and population- based association studies. However, Hemmings et al.28 did not find any association between EcoRV of the MAOA gene and OCD. In Korea, we recruited 121 OCD patients (81 males and 40 females) and 276 controls (138 males and 138 females). In Korea, we found that male OCD patients had a higher frequency of 3-repeats of MAOA-uVNTR than normal male controls (64.2% in OCD vs. 47.8% in control, unpublished), but we did not find this association in female OCD patients. Although more larger-scale studies are warranted, our results (including several previous studies82,89) indicate the possibility of an associa- tion between the MAOA gene and OCD and its gender dismorphic effects. Other genes In addition to monoamines, there have been other putative neurotransmitters or neurotrophic factors playing a role in the development of OCD, such as glutamate, GABA, and brain-derived neurotrophic factor (BDNF). Using the family based association test, Arnold et al.90 tested for an association of the glutamate receptor, ionotrophic, N-methyl-d-aspartate 2B (GRIN2B) with OCD in 130 families and found that GRIN2B may be associated with a suscepti- bility to OCD. Regarding glutamate receptor ionotropic kainate 2 (GRIK2) and 3 (GRIK3), Delorme et al.91 performed a case-control study in 156 patients and 141 controls, and also a transmis- sion disequilibrium test in 124 parent-offspring trios. Although there were no associations of GRIK3 S301A or GRIK2 rs2227281 (intron 14) and rs2227283 (exon 15) with OCD in the case-control or family-based analyses, the GRIK2 SNP l867 allele (rs2238076) in exon 16 was transmitted less than expected in OCD. Recently, there has been increasing evidence that the major inhibitory neurotransmitter, GABA,