A total of 575 subjects were enrolled in this study in which 233 were schizophrenic patients (110 males and 123 females) and 342 were healthy controls (160 males and 182 females). There was no significant difference in gender (c2 = 0.041, R= 0.084) and age (c2 = 1.858, R= 0.064) distribution between the two groups (Table2). All the 6 SNPs were in Hardy-Weinberg Equilibrium in both case group and control group.
Comparison of allele and genotype frequencies between case group and control group
There was statistically significant difference in the allele frequencies distribution of EAAT1 rs2731880 (c2 = 4.205, R= 0.040) and EAAT2 rs12294045 (c2 = 8.144, R= 0.004) between case and control group, and the mutant allele T was significantly increased in the case group. There were no statistical differences in allele frequencies distribution of rs2269272 of EAAT1 gene and rs3088168, rs10836387 and rs12360706 of EAAT2 gene between the two groups. The allele frequencies comparison results of 6 polymorphic loci are shown in table 3.
By comparing the genotype frequencies of the 6 loci in the case and control group, we found that the genotype frequencies distribution of EAAT2 rs12294045 (c2 = 8.054, R= 0.018) were significantly different between the two groups. In the case group, the wild homozygous CC genotype was reduced, while the heterozygous CT genotype was increased. There was no significant difference in genotype frequencies of rs2269272, rs2731880 of EAAT1 gene and rs3088168, rs10836387, rs12360706 of EAAT2 gene between the two groups. The results of genotype frequencies comparison of 6 loci are shown in table 4.
Comparison of clinical features and symptom severity in patients with different genotypes of rs12294045
According to the above results, we found that the polymorphism of EAAT2 rs12294045 was significantly associated with schizophrenia. Therefore, we further examined the differences among three genotypes of rs12294045 in the clinical data and symptom characteristics of patients with schizophrenia. The clinical characteristics included 9 aspects which were gender, age of onset, onset form, duration, family history of psychosis, interpersonal relationship, premorbid characteristics, current marital status and occupational status. The PANSS total score and factor scores were compared as well. We found that there was significant difference among the three genotypes of rs12294045 in family history. Compared with patients without family history, patients with family history of psychosis had lower proportion of CC wild genotype and higher proportion of CT heterozygous genotype. There was no significant difference among the three genotypes of rs12294045 in the other 8 clinical characteristics and the total score and factor scores of PANSS. The comparison of 9clinical characteristics and PANSS scores in patients with different genotypes of rs12294045 is shown in table 5.
Comparison of cognitive test scores in patients with different genotypes of rs12294045 locus
Covariance analysis was then performed to find out whether different genotypes of rs12294045 were related to cognitive function of schizophrenia patients. We regarded family history ( Positive = 1, Negative = 2) as a covariate, cognitive test results as the dependent variables, rs12294045 locus of different genotype groups as a fixed factor, and compared them in multiple comparisons. The results showed that there were statistically significant differences in the verbal learning and number sequence among patients with different genotypes. LSD analysis showed that the verbal learning scores of patients with CT genotypes were significantly lower than those of TT genotypes. In addition, patients with CT genotypes had significantly lower scores than those with CC and TT genotypes in terms of number sequence representing working operational memory. There were no statistical differences in the scores of connection, coding symbol, spatial breadth, maze test, visual test, processing fluency, emotional control, and continuous work among patients with different genotypes of rs12294045. The comparison of cognitive test scores among patients with different genotypes of rs12294045 is shown in table 6.