Association Study Of Genetic Polymorphisms In Serotonin System And Family Environment With Antisocial Personality Disorder

ObjectiveThe aim of the present study was to identify the genotype and allele frequencies of susceptible genes involving in 5-hydroxytryptamine transporter (5-HTT), monoamine oxidase A (MAOA) and tryptophan hydroxylase 2 (TPH2) in a Chinese Han population, verify and explore the relationship between TPH2 haplotypes, family environment and antisocial personality disorder (ASPD) and to develop approaches for early diagnosis, further understanding pathogenic mechanism of ASPD.MethodsCase-control study, variable number of tandem repeats (VNTR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method were used to detect the polymorphisms of 5-HTT, MAOA rs1137070, TPH2 rs4570625, TPH2 rs4131347, TPH2 rs4290270, TPH2 rs7305115 in 117 ASPD patients and 142 healthy controls. Barratt impulsiveness scale-11 (BIS-11) and family environment scale-Chinese version (FES-CV) were used to evaluate the impulsivity and family environment of all subjects, respectively. The software SHEsis was used to analyze the linkage disequilibrium and haplotypes between the two groups.Results1. The scores of BIS-11 and its factors in ASPD group were higher than the health control group, but only the attention, no-plan factor score and BIS-11 total scores between the two groups were statistically significant (P<0.05). The scores of expressiveness in ASPD group was significantly lower than the health control group, wherever the scores of conflict, achievement orientation and control were significantly higher than the health control group (P<0.05).2. The distribution of 5-HTT and MAOA rs1137070 genotypes followed Hardy-Weinberg equilibrium among ASPD patients and control subjects (P>0.05 for each comparison). Our data showed that the distribution of 5-HTT and MAOA alleles and genotypes were not significantly different in patients compared with controls. 5-HTT VNTR interacted with MAOA rs1137070 significantly increases the risk with ASPD.3. The distribution of TPH2 rs4570625, rs4131347, rs4290270, rs7305115 genotypes followed Hardy-Weinberg equilibrium among patients and control subjects. There were significant differences between ASPD and controls on genotype and allele frequencies of TPH2 rs4570625(χ~2=7.73, P< 0.05;χ~2=5.12, P<0.05). The GG genotype and G allele were positively associated with ASPD [odds ratio (OR) =1.458, 95% confidence interval (CI) =1.080-1.968; OR=1.479, 95%CI=1.045-2.094]. However, the current study did not demonstrate any significant difference in genotypes and alleles frequencies of other three SNPs between patients and controls.4. The presence of TA haplotype of TPH2 rs4290270-rs7305115 was significantly more frequent in cases than in controls [P<0.05; OR1.865; 95%CI 1.135-3.065]. The other haplotypes did not show significant difference between patients and controls.5. The scores of BIS-11 and its factors in GG genotype group [(71.28±7.50), (19.60±3.41), (25.73±4.92), (25.95±4.77)]were higher than GT genotype group [(66.23±8.06), (17.79±3.02), (23.06±3.84), (25.38±4.97)] and TT genotype group [(66.55±8.49), (18.50±3.35), (23.45±4.08), (24.97±4.90)], but only the difference of BIS-11 total scores, the attention and motor factor scores among three groups were statistically significant (F<0.05). The scores of BIS-11 and its factors in G allele group [(68.52±8.17), (18.61±3.31), (24.27±4.54), (25.64±4.86)] were higher than no G genotype group [(66.55±8.49), (18.14±3.50), (23.44±4.07), (24.97±4.90)], however, there were no statistical significance between two groups.6. Interactions between genetic and environmental (G×E) revealed that expressiveness, achievement, orientation and control increased the risk of ASPD in the presence of T allele of TPH2 rs4570625 (OR 1.122, 0.843, 1.080 and 0.880, respectively; 95%CI 1.043-1.206, 0.747-0.951, 1.010-1.155 and 0.792-0.978, respectively.) and the expressiveness and moral-religious emphasis increased the risk of ASPD in the presence of TA haplotype (P<0.05; OR1.122, 95% CI1.043-1.206; OR1.080, 95% CI1.010-1.155).Conclusions1. 5-HTT,MAOA SNPs did not show to be a risk factor for ASPD. Interaction between 5-HTTVNTR and MAOA rs1137070 increases the risk with ASPD.2. TPH2 rs4570625 polymorphism may be association with ASPD in Chinese Han population. The GG genotype and G allele may be the risk factors of ASPD and impulsivity.3. TA haplotype of TPH2 rs4290270-rs7305115 might influence the susceptibility for ASPD and adversity family environments might increase the risk of ASPD in the presence of risk allele or haplotype.