Istically significant difference between 2 genotype groups (C/C vs C/T, C/C vs T/T) (post-hoc analysis; LSD) (p,0.05). doi:10.1371/journal.pone.0060340.gx2 = 11.595 and p = 0.003, and x2 = 6.194, p = 0.045, respectively). However, there was no significant difference in the distribution of rs2030324 genotypic frequencies between subjects with high and low LDAEP at C3 (p = 0.093) and Fz (p = 0.376). The distribution of rs1491850 genotypic frequencies differed inhibitor significantly between subjects with high and low LDAEP at Pz (x2 = 6.392, p = 0.041). The frequencies of all three BDNF markers (rs6265, rs2030324, and rs1491850) at Pz were higher for subjects with a high LDAEP than for those with a 
low LDAEP. The mean LDEAP was significantly higher for female subjects than for male subjects only at C3 (t = ?.671, p = 0.008), with there being no gender differences in the LDAEP at Cz, Pz, Fz, and C4.Figure 2. Comparison of LDAEP at C3 among genotypes of rs2030324. Mean values were presented as horizontal bars. There was a significant difference among 3 genotype groups (ANOVA) (p,0.05). There was a statistically significant difference between 2 genotype groups (C/C vs C/T, C/C vs T/T) (post-hoc analysis; LSD) (p,0.05). doi:10.1371/journal.pone.0060340.ggenotype in post-hoc analysis (least-squares difference, p = 0.054). These results indicate that the serotonergic activity is lower in the Val/Met genotype group than in Val/Val. In addition, there were significant differences in the distribution of genotypic frequencies between subjects with high and low LDAEP at Pz (rs6265) (table 1). In particular, rs6265 Val/Met genotype group had more subjects with relatively high LDAEP than other groups.Haplotype analysisThe overall haplotype (rs6265, rs2030324, and rs1491850) frequencies did not differ significantly between the low- and highLDAEP groups at Cz and Pz, although the frequency of one haplotype (A-C-T) did differ significantly between the low- and high-LDAEP groups at Cz (43 vs. 22 , respectively; p = 0.014; Table S3, S4). However, the frequencies of the rs2030324- and rs1491850-containing haplotypes differed significantly between the low- and high-LDAEP groups at Pz (p = 0.017; Table 2). The frequency of one haplotype (C-T) differed significantly between the low- and high-LDAEP groups at Cz (55 vs. 42 , respectively; p = 0.000; Table 2).DiscussionThis was a replication study, in that it had the same design as that of Juckel and colleagues [20]. However, this is the first study to show an association between 
BDNF SNPs [rs6265(Val/Met), rs2030324, and rs1491850] and the LDAEP in an Asian population. We found that the LDAEP at Pz differed significantly among the rs1491850 and rs2030324 genotype groups (table 1), and although we did not find significant differences in the LDAEP at Pz among the rs6265 genotype groups (in ANOVA), we did Autophagy observe a trend indicating that the LDAEP of the Val/Met (A/G) genotype group was higher than that of the Val/Val (G/G)Figure 3. Comparison of LDAEP at Pz among genotypes of rs1491850. Mean values were presented as horizontal bars. There was a significant difference among 3 genotype groups (ANOVA) (p,0.05). There was a statistically significant difference between 2 genotype groups (C/C vs T/T) (post-hoc analysis; LSD) (p,0.05). doi:10.1371/journal.pone.0060340.gBDNF Gene and LDAEPTable 1. Statistical analyses on the intensity of LDAEP with genotypes of the three SNPs in BDNF gene and the distribution of genotypic frequenc.Istically significant difference between 2 genotype groups (C/C vs C/T, C/C vs T/T) (post-hoc analysis; LSD) (p,0.05). doi:10.1371/journal.pone.0060340.gx2 = 11.595 and p = 0.003, and x2 = 6.194, p = 0.045, respectively). However, there was no significant difference in the distribution of rs2030324 genotypic frequencies between subjects with high and low LDAEP at C3 (p = 0.093) and Fz (p = 0.376). The distribution of rs1491850 genotypic frequencies differed significantly between subjects with high and low LDAEP at Pz (x2 = 6.392, p = 0.041). The frequencies of all three BDNF markers (rs6265, rs2030324, and rs1491850) at Pz were higher for subjects with a high LDAEP than for those with a low LDAEP. The mean LDEAP was significantly higher for female subjects than for male subjects only at C3 (t = ?.671, p = 0.008), with there being no gender differences in the LDAEP at Cz, Pz, Fz, and C4.Figure 2. Comparison of LDAEP at C3 among genotypes of rs2030324. Mean values were presented as horizontal bars. There was a significant difference among 3 genotype groups (ANOVA) (p,0.05). There was a statistically significant difference between 2 genotype groups (C/C vs C/T, C/C vs T/T) (post-hoc analysis; LSD) (p,0.05). doi:10.1371/journal.pone.0060340.ggenotype in post-hoc analysis (least-squares difference, p = 0.054). These results indicate that the serotonergic activity is lower in the Val/Met genotype group than in Val/Val. In addition, there were significant differences in the distribution of genotypic frequencies between subjects with high and low LDAEP at Pz (rs6265) (table 1). In particular, rs6265 Val/Met genotype group had more subjects with relatively high LDAEP than other groups.Haplotype analysisThe overall haplotype (rs6265, rs2030324, and rs1491850) frequencies did not differ significantly between the low- and highLDAEP groups at Cz and Pz, although the frequency of one haplotype (A-C-T) did differ significantly between the low- and high-LDAEP groups at Cz (43 vs. 22 , respectively; p = 0.014; Table S3, S4). However, the frequencies of the rs2030324- and rs1491850-containing haplotypes differed significantly between the low- and high-LDAEP groups at Pz (p = 0.017; Table 2). The frequency of one haplotype (C-T) differed significantly between the low- and high-LDAEP groups at Cz (55 vs. 42 , respectively; p = 0.000; Table 2).DiscussionThis was a replication study, in that it had the same design as that of Juckel and colleagues [20]. However, this is the first study to show an association between BDNF SNPs [rs6265(Val/Met), rs2030324, and rs1491850] and the LDAEP in an Asian population. We found that the LDAEP at Pz differed significantly among the rs1491850 and rs2030324 genotype groups (table 1), and although we did not find significant differences in the LDAEP at Pz among the rs6265 genotype groups (in ANOVA), we did observe a trend indicating that the LDAEP of the Val/Met (A/G) genotype group was higher than that of the Val/Val (G/G)Figure 3. Comparison of LDAEP at Pz among genotypes of rs1491850. Mean values were presented as horizontal bars. There was a significant difference among 3 genotype groups (ANOVA) (p,0.05). There was a statistically significant difference between 2 genotype groups (C/C vs T/T) (post-hoc analysis; LSD) (p,0.05). doi:10.1371/journal.pone.0060340.gBDNF Gene and LDAEPTable 1. Statistical analyses on the intensity of LDAEP with genotypes of the three SNPs in BDNF gene and the distribution of genotypic frequenc.