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
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国家自然科学基金(81660233、81360209、81960258);新疆医科大学创新创业项目(CXCY2017031)


Association between ZNF804A polymorphism and severity of psychiatric symptom of Uighur firstepisode schizophrenic patients
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    摘要:

    目的 了解锌指蛋白 804A基因(ZNF804A)基因rs13009002、rs72893068、rs61739291 3 个 位点的基因多态性,并分析与维吾尔族首发精神分裂症患者精神症状严重程度的关系。方法 于2015年 7 月至 2018 年 6 月,选取新疆维吾尔自治区喀什、和田精神卫生机构及新疆医科大学第一附属医院精 神科收治的 937 例维吾尔族首发精神分裂症患者以及 937 名健康体检者为病例组和对照组。采用 PANSS 评估病例组精神症状的严重程度。采用高通量基因测序技术对两组ZNF804A基因 rs13009002、 rs72893068、rs61739291 3 个位点进行测序分析,并对关联位点进行性别比较,比较基因多态性与精神症 状严重程度。结果 两组受试者 rs72893068 和 rs61739291 位点的基因型和基因频率比较,差异无统计 学意义(P> 0.05)。两组受试者 rs13009002 位点 G 基因频率为 92.2%(1 728/1 874),高于对照组的 90.2% (1 690/1 874),差异有统计学意义(χ2 =4.798,P< 0.05)。两组受试者 rs13009002 位点显性[OR(95%CI)= 1.30(1.02~1.66)]、超显性[OR(95%CI)=1.28(1.00~1.63)]和加性[OR(95%CI)=1.31(1.03~1.65)]遗传 模式比较,差异有统计学意义(P< 0.05)。在男性受试者中,病例组 rs13009002 位点显性 GG 基因型、超 显性 GG/TT 基因型多于对照组,差异有统计学意义(χ2 =11.944、11.645;P< 0.01)。在男性受试者中, 病例组 G 基因频率高于对照组,差异有统计学意义(χ2 =11.020,P< 0.01)。男性患者阴性症状得分高 于女性,一般精神病理、抑郁和激活性得分低于女性,差异有统计学意义(t=2.003、2.023、3.296、2.736; P< 0.05);青年、中年、老年患者的阳性症状和思维障碍得分比较,差异有统计学意义(F=4.136、5.238; P< 0.05)。病例组 rs13009002 显性 GG 基因型男性患者的阳性症状、思维障碍得分高于 GT/TT 基因型, 差异有统计学意义(t=2.970、2.260;P< 0.05);超显性 GG/TT 基因型男性患者的阳性症状、思维障碍和攻 击性得分高于 GT 基因型患者,差异有统计学意义(t=2.776、2.244、2.110; P< 0.05)。结论 ZNF804A基 因 rs13009002 位点与我国维吾尔族首发精神分裂症的易感性相关,与男性患者精神症状严重程度相关, 携带显性 GG 和超显性 GG/TT 基因型患者的阳性精神症状较严重。rs72893068、rs61739291 位点与我国 维吾尔族人群精神分裂症缺乏关联性。

    Abstract:

    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.

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  • 在线发布日期: 2023-03-10