The associations of DRD4 rs1800955 and DRD4 CpG2.3 unit methylation with the prevalence of the paranoid symptoms.
Three SNPs of DRD4 and 5 SNPs of COMT were analyzed in our study, but only the genotype distribution of DRD4 rs1800955 was significantly different between the groups with and without MA-induced paranoid symptoms (χ2=4.268, p=0.039) (Table 2). MAUD patients carrying the major allele (TT) of DRD4 rs1800955 had a significantly higher proportion of MA-induced paranoid symptoms (51.47%) than those carrying the minor C allele (CC and CT individuals: C carriers) (35.58%) (Figure 1A). However, there was no difference in the methylation level of DRD4 between these two groups (TT & C carriers; z=-1.668, p=0.0955) (Figure 1B). Because the methylation level of DRD4 showed no significant difference between patients with and without paranoid symptoms (z=-0.400, p=0.689, Figure 1C), we further compared the methylation degrees of all 35 DRD4 CpG units. Figure 1D and 1E show that the methylation degrees of CpG_2.3 in the promoter region of the DRD4 gene were lower in patients with MA-induced paranoid symptoms compared to those without paranoid symptoms (z=-2.273, p= 0.023), and this difference was mainly driven by MAUD patients carrying C alleles (z=-1.994, p=0.046). The interaction of DRD4 rs1800955 C allele and decreased DRD4 CpG2.3 methylation degree contributed to the lower prevalence of the paranoid symptom (Figure 1F).