Association Between The Genes Polymorphisms In BDNF Signal Pathways And Personality

Objective To explore the single role of the genes such as BDNF,PKB1,GSK-3B and PRKCG in brain-derived neurotrophic factor (BDNF) pathways, and search for the interaction effects among them on the personality in Chinese North Han health population.Methods 317 unrelated Chinese Han health people were selected with strict standards. All subjects were assessed by Eysenck Personality Quesrionnaire (EPQ) including three personality dimensions: Neuroticism(N), Introversion-Extraversion(E) and Psychoticism(P). We calculated the standard scores (T) of three dimensions, and then divided N, E dimensions into three levels by the T38.5~61.5: Non-neuroticism, moderate and Neuroticism; Introversion, moderate and Extraversion; divided P dimensions into two levels by the T61.5: Psychoticism and Non-psychoticism. Six single nucleotide polymorphisms (SNPs) of BDNF pathways genes were detected by polymerase chain reaction (PCR), including rs6265 and rs7124442 in BDNF gene, rs2494746 and rs2494738 in PKB1 gene, rs6782799 in GSK-3B gene, and rs3745406 in PRKCG gene. SPSS13.0 software were used for monofactorial analyses: Personality means were compared with t-test and One-Way ANOVA, the genotypic and allelic frequency distribution were compared withχ2 analysis; UNPHASED program were used to perform the gene-gene interaction analysis among SNPs.Results:1. Hardy-Weinberg equilibrium testThe goodness-of-fitχ2 test for Hardy-Weinberg equilibrium showed that the genotypic distributions of 5 SNPs (rs6265 and rs7124442 in BDNF gene, rs2494746 in PKB1, rs6782799 in GSK3B, and rs3745406 in PRKCG) in this sample were in HWE (P>0.05), which indicated that the sample can represent the population. However, rs2494738 in PKB1 significantly deviated from the Hardy–Weinberg equilibrium (P<0.05), and was excluded from following analysis.2. General demography data analysisThere were no significant difference in distributions of mean age,sex and educational background between different personality groups(P>0.05).3. Single gene analyses3.1 BDNF rs6265①No statistically significant difference of each personality dimension mean was detected between different rs6265 genotypes and alleles(P>0.05). ②There was no significant difference of rs6265 genotypes and alleles frequency distribution between different personality dimension groups(P>0.05).3.2 BDNF rs7124442①The difference of E personality dimension mean was not statistically significant between different rs7124442 genotypes (P>0.05). E dimension mean with allele T(56.36±10.79) was lower than with allele C(60.19±11.39), which was statistically significant(t=1.977, P=0.048), but it showed no significant after Bonferroni correction(P>0.05). N,P dimensions mean was not statistically significant between rs7124442 genotypes (P>0.05).②T here was no statistically significant difference of rs7124442 genotypes and alleles frequency distribution between variant personality dimension groups(P>0.05).3.3 PKB1 rs2494746①No statistically significant difference of each personality dimension mean was detected between different rs2494746 genotypes and alleles(P>0.05).②T here was no statistically significant difference of rs2494746 genotypes and alleles frequency distribution between different personality dimension groups(P>0.05).3.4 GSK-3B rs6782799①No statistically significant difference of each personality dimension means was detected between different rs6782799 genotypes and alleles(P>0.05).②There was no statistically significant difference of rs6782799 genotypes and alleles frequency distribution between different personality dimension groups(P>0.05).3.5 PRKCG rs3745406①No statistically significant difference of each personality dimension means was detected between different rs3745406 genotypes and alleles(P>0.05).②The frequency distribution of rs3745406 allele A in psychoticism group (47.4%) was more than no psychoticism group(30.4%), which was significant (χ2=4.793,P=0.029). But it showed no significant after Bonferroni correction(P>0.05). There was no statistically significant difference of rs3745406 alleles frequency distribution between N or E personality dimension groups(P>0.05). No significant difference of rs3745406 genotypes frequency distribution was detected between different personality dimension groups(P>0.05).4. Interaction effects gene-gene analysisUNPHASED results showed that the significant interaction effects were detected for the GSK3B rs6782799-PRKCG rs3745406 combination (χ2=15.99, P=0.0252), the PRKCG rs3745406-BDNF rs7124442 combination (χ2=9.859, P=0.043) in Psychoticism dimension; and the GSK3B rs6782799-PRKCG rs3745406 combination (χ2=12.39, P=0.015) in Introversion-Extraversion personality dimension. After 1000 times repeating by the permutation testing, the P value of the GSK3B rs6782799-PRKCG rs3745406 combination, and the GSK3B rs6782799-PRKCG rs3745406 combination remained significant(P<0.05), but the P value of the PRKCG rs3745406-BDNF rs7124442 combination turned negative (P>0.05). In the Neuroticism personality, there are no interaction effects found to be significant (P>0.05).Conclusions:1. No significant associations were found between BDNF,PKB1,GSK-3B,PRKCG single gene and EPQ personality in Chinese Han health population.2. The two interaction effects were detected including BDNF rs7124442 and PRKCG rs3745406 on Introversion-Extraversion personality, GSK-3B rs6782799 and PRKCG rs3745406 on Psychoticism dimension in Chinese Han health population.