Genetics of Obsessive-Compulsive Disorder genotyped and phenotyped both 124 OCD patients and 171 normal controls but could not find any association between 5-HTTLPR polymor- phism and the development of OCD. However, in the OCD group, patients with the L/L + S/L geno- type had higher scores for the religious/somatic factor derived from 13 main contents of the Yale- Brown obsessive-compulsive symptom (Y-BOCS) checklist than those with the S/S genotype.42 The frequencies for the 5-HTTLPR genotype in our sample revealed a higher percentage (63 - 64%) of the S/S genotype and a very lower percentage (3%) of the L/L genotype, which were quite dif- ferent from those determined from a Western pop- ulation, where a higher percentage (32 - 47%) of the L/L genotype and a relatively lower percent- age (14 - 15%) of the S/S genotype were found.35 Recently, other single-nucleotide variants have been detected within HTTLPR,43 and one of them is an A G SNP which is located 1,629 bp up- stream of the transcription start point. Because this G is a sequence variation that always occurs in the context of the L allele of HTTLPR in which it alters AP2 transcription factor binding and suppresses transcription, the A and G alleles are referred to as LA and LG. Therefore, the two L alleles LA and LG, together with the S allele, comprise a triallelic locus of 5-HTTLPR,44 and unrecognized LG alleles in S/L and L/L genotypes can create the appear- ance of S allele dominance because certain LG- containing genotypes tend not to be high ex- pressing.44 Hu et al.44 reported that the gain-of- function LALA genotype was approximately twice as common in 169 whites with OCD than in 253 ethnically matched controls, which means it has a moderate (1.8 fold) effect on the risk of OCD. They also analyzed a TDT test using 175 trios consisting of probands with OCD and their parents, and they found that the LA allele was overtransmitted to the patients with OCD by twofold. Serotonin receptor genes Among many serotonin receptor subtypes, the 5-HT2A receptor has been the most important in the etiology and treatment of OCD. The activation of postsynaptic 5-HT2A and 5-HT2C receptors may be important in the improvement of OCD symptoms after treatment with an SSRI.45 Studies in OCD patients showed blunted prolactin and cortisol responses to 5-HT2 receptor agonists.46 Enoch et al.47 recruited and genotyped 101 Cau- casian OCD patients (48 females, 53 males) and 138 control subjects (77 females, 61 males) and found that the -1438A allele frequency was higher only in female OCD patients and not in male patients. Walitza et al.48 performed an association analysis of 5-HT2A polymorphism in 55 German children and adolescents with OCD, and also in 223 controls, and confirmed the association between the -1438A allele of the 5-HT2A gene and juvenile OCD. Meira-Lima et al.49 examined the allelic and genotypic frequencies of the T102C and C516T variants of the 5-HT2A gene in 79 Brazilian OCD patients and 202 control subjects. Although they did not find any significant differences in the frequencies of allele and genotype for the T102C 5-HT2A gene polymorphism, they found a sig- nificant association between C516T 5-HT2A gene polymorphism and OCD. Tot et al.50 analyzed 58 Turkish OCD patients and 83 controls. Although they could not find significant differences in geno- type distribution for either T102C or -1438 G/A polymorphism of 5-HT2A between the two groups, they found that the TT genotype for T102C and AA genotype for -1438 G/A polymor- phism of 5-HT2A were significantly higher in the patients with severe OCD compared to those with moderate to severe OCD. Other studies did not find a significant association between -1438 A/G polymorphism28,38,51 or T102 polymorphism28 and OCD. Some researchers have found that the activation of the 5-HT2C receptor induces self-grooming in rats.52 This result supports the hypothesis that selective stimulation of central 5-HT2C receptors exacerbates symptoms in OCD. It has also been reported that m-CPP, which stimulates 5-HT2C receptor, exacerbates OC symptoms.30,31 Theses studies provide support for the possible involve- ment of 5-HT2C receptors in the etiology of OCD. Cavallini et al.53 investigated the role of the Cys23Ser mutation of the 5-HT2C receptor gene in OCD by performing an association study com- paring a sample of 109 Italian OCD patients with a sample of 107 healthy control subjects. However, they did not find any allelic or genotypic associa- tion between OCD and the 5-HT2C receptor gene. Frisch et al.38 also performed a similar study in Yonsei Med J Vol. 47, No. 4, 2006