Association Study On The Serum Level Of GABA And The GABRA4 Gene Polymorphism With Childhood Autism

Objective(1) The purpose of this study was to explore the pathophysiological mechanism of childhood autism determined by the serum level of gamma-aminobutyric acid (GABA), and explore the relationship between the serum level of GABA and the characteristics of autism, the severity of the disease.(2) The purpose of this study was to explore the relationship between Henan Province Han GABRA4 gene polymorphisms and childhood autism by detecting two single-nucleotide polymorphisms (SNPs) including rs1912960,rs2229940 located on GABRA4.Methods(1) The sera level of GABA was measured with enzyme linked immunosor-bent assay (ELISA) in 35 patients with childhood autism and compared with that of 35 control children. Childhood Autism Rating Scale (CARS) was administered to assess the severity of the disease.(2) The two SNPs, rs1912960,rs2229940 on GABRA4 were genotyped by PCR-RFLP in 49 autism children,94 parents, and 158 controls in Chinese Han. The family-based transmission disquilibrium test (TDT) and case-control association study were performaed at the same time. To analysis the difference in the level of GABA and the CARS scores in different genotypes of patients.(3) To check the accuracy of the allele identified technique in PCR-RFLP by DNA sequencing.(4) GENEHUNTER (version 2.4) was used in TDT. The Haploview 4.1 was used in haplotype and all analyses were conducted with SPSS 13.0 for Windows, a=0.05 is the significance level. Results(1) The sera level of GABA was significantly higher in autism patients (1.23±0.28μmol/L) than that in controls(1.07±0.29μmol/L)(t=2.513, P<0.05).(2) No significant difference was found in the level of GABA between the subgroups with different CARS scores, mild-medium group:(1.31±0.25μmol/L), severe group:(1.17±0.29μmol/L) (t=1.534, P>0.05).(3) No significant difference was found in the level of GABA and the gender of the patients (t=-0.368, P>0.05).(4) There was no significant correlation between the level of GABA and the total scores of CARS (r=-0.109, P>0.05). There was a significant positive correlation between the level of GABA and the visual response (r=0.344,P<0.05).(5) There was no significant correlation between the level of GABA and the age of the patients (r=-0.288, P>0.05). There was a significant negative correlation between the level of GABA and the duration of the patients (r=-0.382, P<0.05).(6) No significant differences were found on family-based TDT for single-locus marker in two SNPs in autism (P>0.05). There was no significant transmission disequilibrium in all the four haplotypes.(7) All these two SNPs (rs1912960, rs2229940) among control samples met Hardy-Weinberg equilibrium. In case-control association analysis, rs2229940 have significant differences were found in allelic (χ2=4.128, P<0.05) and genotypic (χ2=9.438, P<0.05) distribution of the two SNPs between autism group and control group.(8) There was no significant difference in frequeney of haplotypes between autism and control group (P>0.05).(9) There was a significant difference in CARS scores in different genotypes of rs2229940 and in relationships scores of subscale between genotype C/C and C/A (P<0.05), but no significant difference in the other subscales'scores between different genotypes (P>0.05).There was no significant difference in CARS scores in different genotypes of rs 1912960 (P>0.05).(10) There was no significant difference in GABA level between different genetypes of the two SNPs (P>0.05). Conclusions(1) The serum level of GAB A may be a kind of biochemistric trait in a subgroup of childhood autism, and it have influence on the visual response of autism children.(2) GABRA4 gene may have association with Henan Province Han childhood autism.