Association of regulator of G protein signaling 4 gene polymorphism and methylation with schizophrenia / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To explore the differences of regulator of G protein signaling 4 (RGS4) gene polymorphisms and methylation between schizophrenia and healthy controls, as well as the association between gene polymorphisms and methylation.Methods:A total of 129 schizophrenia patients and 131 healthy controls from Southen Fujian were enrolled in this study. The peripheral blood DNA of all the subjects was extracted.The three polymorphic loci of RGS4 (rs10759, rs12753561 and rs951436) were amplified, sequenced, and then genotyped. In addition, 32 subjects were randomly selected from the two groups respectively and the gene methylation level of RGS4 was detected by sequencing after bisulfite treatment. SPSS 20.0 software was used for data analysis. The χ2 test and independent sample t-test were used to analyze the difference of gene methylation of RGS4.Two-way ANOVA was used to analyze the association between RGS4 gene polymorphism and methylation. Results:There were three genotypes of AA, AC and CC for rs10759 locus in the subjects of patient group and control group. And the distribution difference of genotypes between the two groups was statistically significant ( χ2=6.431, P=0.040), but there was no significant difference in allele frequency( χ2=1.270, P=0.260). For rs12753561, there were three genotypes of GG, GT and TT, and their distribution of genotypes was significantly different ( χ2=6.217, P=0.045). There was no significant difference for the allele frequency for rs12753561( χ2=0.021, P=0.885). For rs951436, there were three genotypes of AA, AC and CC, and there were no significant difference in genotype distribution and allele frequency distribution between the two groups( χ2=0.008, 0.007, both P>0.05). Methylated CpG sites were found in 26 patients and 27 healthy controls, and these were no significant difference between the two groups( χ2=0.110, P=0.740). There was no significant difference ( t=-0.318, P=0.752) of individual methylation rate (number of methylation sites/10) between schizophrenia patient group (0.24±0.11) and healthy control group (0.26±0.18). There was also no significant difference of methylation rate between male and female in both groups(both P>0.05). Finally, there was no significant difference of individual methylation rate among rs10759, rs12753561 and rs951436 genotypes (all P>0.05). Conclusion:RGS4 rs10759 and rs12753561 genotypes may be involved in schizophrenia, while RGS4 gene methylation has no association with schizophrenia. In addition, RGS4 gene polymorphism has no association with the methylation in the current experimental setting.