CLINICS 2012;67(4):335-340 HWE program (12). The analysis was performed using EpiInfo version 6.0 and SPSS version 15.0. ETHICS The protocol was in accordance with Declaration of Helsinki for research with human subjects and approved by the Ethics Committee at the Hospital das Cl´ınicas, University of Sa˜o Paulo Medical School (CAPPesq). All subjects gave written, informed and free consent. RESULTS Hardy-Weinberg Equilibrium The genotypic distributions of the HTR2A C516T, HTR2A T102C, and HTR1B G681C polymorphisms were in Hardy- Weinberg equilibrium (HWE) in the CN (p.0.05). The case group was in HWE for all polymorphisms except for the HTR2A T102C polymorphism (p = 0.0001). Frequency of Polymorphisms Distributions The patient and control polymorphism frequency data are presented in Table 1. In the patients, the 102CC genotype is less frequent than in the CN (p,0.001 after a chi-square partition), and the heterozygosity frequency was higher (p = 0.02), with no difference in the 102TT genotype. The frequency of the T allele was higher in the patients than in the CN (p,0.01). In Table 2, the allele frequency of each DNA marker in the OCD patients group was subdivided into responders versus non-responders for the SRIs. The 516CC genotype was more frequent, and consequently, the heterozygosity frequency was reduced because there were no patients with a 516TT genotype among the non- responders versus the responders (p,0.01). After a chi- square partition, CC homozygosity for the HTR1B G681C polymorphism was more frequent among non-responders versus responders (p = 0.018). Table 1 - Polymorphism frequency among patients and controls. Patients (RP + NR) (%) CN (%) p-value 48 (81.4) 11 (18.6) 0 (0) 17 (28.3) 43* (71.7) 0** (0) 6 (10.2) 24 (40.7) 29 (49.2) 107 (90.7) 11 (9.3) 77 (64.2) 43 (35.8) 36 (30.5) 82 (69.5) 26 (92.9) 2 (7.1) 0 (0) 6 (20.0) 14* (46.7) 10** (33.3) 2 (6.9) 12 (41.4) 15 (51.7) 54 (96.4) 2 (3.6) 26 (43.3) 34 (56.7) 16 (27.6) 42 (72.4) 0.16 ,0.001 0.88 0.18 0.007 0.69 Genotypes HTR2A C516T CC CT TT HTR2A T102C TT TC CC HTR1B G681C CC CG GG Alleles HTR2A C516T C T HTR2A T102C T C HTR1B G681C C G Note: RP = Responders; NR = Non-responders; CN = Controls. *p = 0.02 after a chi-square partition for heterozygosity; **p,0.001 after a chi-square partition for the CC genotype. 5-HT polymorphisms and response to SSRIs in OCD Corregiari FM et al. Table 2 - Polymorphism frequency among non- responders and responders. Genotypes HTR2A C516T CC CT* HTR2A T102C TT TC* HTR1B G 681 C CC CG GG HTR1B G 681 C CC GC or GG Alleles HTR2A C516T C T HTR2A T102C T C HTR1B G681C C G NR (%) 30 (93.8) 2 (6.2) 8 (25.0) 24 (75.0) 6** (18.8) 11 (34.4) 15 (46.9) 6 (18.8) 26 (81.2) 62 (96.9) 2 (3.1) 40 (62.5) 24 (37.5) 23 (35.9) 41 (64.1) RP (%) 18 (66.7) 9 (33.3) 9 (32.1) 19 (67.9) 0** (0) 13 (48.1) 14 (51.9) 0 (0) 27 (100) 45 (83.3) 9 (16.7) 37 (66.1) 19 (33.9) 13 (24.1) 41 (75.9) p-value ,0.01 0.54 0.054 0.018 0.01 0.68 0.16 337 Note: RP = Responders; NR = Non-responders; CN = Control. *No TT genotype for HTR2A C516T and no CC genotype for HTR2A T102C were observed among patients; **p,0.05 for the CC genotype after a chi- square partition. Relationship among genetic polymorphisms, study groups and endocrine/serotonin variables Relationship with basal hormonal/serotonin levels The basal levels of serotonin, prolactin, growth hormone (GH), and cortisol and the interactions with the investigated polymorphisms were compared among the three study groups (NR, RP, and CN). No associations were found among the groups; polymorphisms; and prolactin, GH or cortisol basal levels. The CN showed the highest platelet- rich plasma serotonin concentration (p,0.001). The only significant interaction was observed between the groups and the HTR1B G681C polymorphism (p = 0.022; Table 3), with the highest serotonin level observed among the CC homozygous of the CN (558.01 ng/ml) and the lowest level observed among non-responders with the same genotype (74.68 ng/ml). Relationship with endocrine response to intravenous citalopram Prolactin, GH and cortisol responses to citalopram and interactions with the investigated polymorphisms were compared among the three groups (NR, RP, and CN). As reported previously (4), the prolactin increase (as a percentage of the baseline) was greater in the CN than in the responder and the non-responder groups (p = 0.017 for NR versus CN; p = 0.004 for RP versus CN). However, there was no difference between the responder and the non-responder groups. The prolactin response was not associated with any allele or genotype among the C516T HTR2A and T102C HTR2A polymorphisms. However, the subjects with CC homozygos- ity for the G681C HTR1B polymorphism showed a more intense prolactin response to citalopram (p,0.01 for both CC