Objective To explore the genetic polymorphisms of 3 sites, including rs13009002,rs72893068 and rs61739291, of zinc finger protein 804A gene (ZNF804A), and to analyze the correlation between ZNF804A polymorphism and severity of symptoms in Uighur first-episode schizophrenic patients. Methods From July 2015 to June 2018, a total of 937 Uighur first-episode schizophrenic patients and 937 healthy physical examinees admitted in the Kashgar and Hotan Mental Health Institutions of Xinjiang Uygur Autonomous Region and the Department of Psychiatry of the First Affiliated Hospital of Xinjiang Medical University were selected as the case group and the control group. The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). The 3 loci (rs13009002, rs72893068 and rs61739291) of ZNF804A of the 2 groups were sequenced using high-throughput gene sequencing. The association loci were compared by gender. The gene polymorphisms and severity of psychiatric symptoms were compared. Results There were no significant differences between the case and control groups in genotyping of rs72893068 and rs61739291, or allele frequency (P> 0.05). The G allele frequency of rs13009002 of the case group was 92.2% (1 728/1 874), higher than that of the control group 90.2% (1 690/1 874), and the difference was statistically significant (χ2 =4.026, P < 0.05). The differences in dominant [OR (95%CI)=1.30 (1.02- 1.66)], over-dominant [OR (95%CI)=1.28 (1.00-1.63)], and additive [OR (95%CI)=1.31 (1.03-1.65)] genetic patterns of rs13009002 between the 2 groups were statistically significant (P< 0.05). Among the male subjects, the dominant GG genotype and over-dominant GG/TT genotype at rs13009002 locus in the case group were more than those in the control group, and the differences were statistically significant(χ2 =11.944,11.645;P< 0.01). Among the male subjects, the frequency of G gene in the case group was higher than that in the control group, and the difference was statistically significant (χ2 =11.020, P< 0.01). The score of negative symptoms of male patients was higher than that of female patients, and the score of general pathology, depression and activation was lower than that of female patients, with statistically significant difference (t=2.003,2.023, 3.296, 2.736; P< 0.05). There was statistically significant difference in the scores of positive symptoms and thinking disorders among young, middle-aged and elderly patients (F=1.189,5.238;P< 0.05). The scores of positive symptoms and thinking disorders of male patients with rs13009002 dominant GG genotype in the case group were higher than those with GT/TT genotype, and the difference was statistically significant (t=2.970, 2.260; P<0.05). Male patients with over-dominant GG/TT genotype had higher scores of positive symptoms, thinking disorder and aggression than those with GT genotype, and the difference was statistically significant (t=2.776, 2.244, 2.110; P< 0.05). Conclusions The rs13009002 loci of ZNF804A gene is associated with the susceptibility of the first episode of schizophrenia in the Uygur nationality in China, and with the severity of mental symptoms in male patients. The positive mental symptoms of patients with dominant GG and over-dominant GG/TT genotype are more serious. The rs72893068 and rs61739291 loci lack association with schizophrenia in Chinese Uighurs.
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孙乐乐,史新玉,徐斌,胡红星,母代斌,傅松年,师咏勇,伊琦忠. ZNF804A 基因多态性与维吾尔族首发精神分裂症患者精神症状严重程度的关联研究[J].神经疾病与精神卫生,2023,23(1): DOI :10.3969/j. issn.1009-6574.2023.01.003.