Liansheng Zhao1, Yin Lin2, Guohui Lao2, Yingcheng Wang1, Lijie Guan2, Jinxue Wei1, Zhenxing Yang1, Peiyan Ni1, Xuan Li2, Zeyu Jiang2, Tao Li1, Xiaoyu Hao2, Dongtao Lin3, Liping Cao4, Xiaohong Ma5. 1. Psychiatric Laboratory and Department of Psychiatry, West China Hospital, Sichuan University, No. 1 Keyuan 4 Road, High Tech Parkm, Chengdu 610041, PR China; National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China. 2. Guangzhou Brain Hospital, Affilated Brain Hospital of Guangzhou Medical University, No. 36 Minxin Road, Liwan District, Guangzhou 510370, PR China. 3. Psychiatric Laboratory and Department of Psychiatry, West China Hospital, Sichuan University, No. 1 Keyuan 4 Road, High Tech Parkm, Chengdu 610041, PR China; College of Foreign Languages and Cultures, Sichuan University, Chengdu 610064, PR China. 4. Guangzhou Brain Hospital, Affilated Brain Hospital of Guangzhou Medical University, No. 36 Minxin Road, Liwan District, Guangzhou 510370, PR China. Electronic address: coolliping@hotmail.com. 5. Psychiatric Laboratory and Department of Psychiatry, West China Hospital, Sichuan University, No. 1 Keyuan 4 Road, High Tech Parkm, Chengdu 610041, PR China; National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: maxiaohong@scu.edu.cn.
Abstract
OBJECTIVE: To determine the correlation among the polymorphisms of dopamine receptor genes, cognitive function of Bipolar disorder (BD) patients, and BD. METHODS: Twenty-three Single Nucleotide Polymorphisms (SNPs) of dopamine receptor genes were genotyped using Illumina GoldenGate genotyping assay in 375 patients with bipolar I disorder (BD-I) (patients group) and 475 healthy controls (control group). Cognitive function tests were performed in 158 patients who were clinically stable and 307 healthy controls who were matched with the patients in age, sex, and education. RESULTS: The allele frequencies of rs3758653 in the promoter region of the DRD4 gene were significantly different between patients group and control group (χ(2)=9.386, Corrected P=0.046). This significant difference was also observed between BD-I patients with psychotic symptoms and healthy controls (χ(2)=9.27, Corrected P=0.049). Patients with BD-I performed significantly worse than healthy controls in all cognitive domains (p<0.01) except TMTA errors and illegal time. Significant interactions between polymorphisms of rs5326 in DRD1 gene and phenotype (affected or unaffected with BD-I) were found in non-perseverative errors (β=3.20 and Corrected P=0.0034) on the Wisconsin Card Sorting Test (WCST). The allele of this SNP denoted the positive effect on the WCST non-perseverative errors in BD-I patients group (β=2.80 and Corrected P=0.017). The genotypic association analyses also supported the findings (F=4.24 and P=0.007), but this effect was not found in controls. LIMITATIONS: The sample size was relatively small and the SNP coverage was limited, making it very important to be cautious when drawing a conclusion. CONCLUSIONS: DRD4 gene may play an important role in psychotic symptomatology rather than in unique diagnosis, BD, for example. A genetic association exists between DRD1 gene and impaired cognition in BD.
OBJECTIVE: To determine the correlation among the polymorphisms of dopamine receptor genes, cognitive function of Bipolar disorder (BD) patients, and BD. METHODS: Twenty-three Single Nucleotide Polymorphisms (SNPs) of dopamine receptor genes were genotyped using Illumina GoldenGate genotyping assay in 375 patients with bipolar I disorder (BD-I) (patients group) and 475 healthy controls (control group). Cognitive function tests were performed in 158 patients who were clinically stable and 307 healthy controls who were matched with the patients in age, sex, and education. RESULTS: The allele frequencies of rs3758653 in the promoter region of the DRD4 gene were significantly different between patients group and control group (χ(2)=9.386, Corrected P=0.046). This significant difference was also observed between BD-I patients with psychotic symptoms and healthy controls (χ(2)=9.27, Corrected P=0.049). Patients with BD-I performed significantly worse than healthy controls in all cognitive domains (p<0.01) except TMTA errors and illegal time. Significant interactions between polymorphisms of rs5326 in DRD1 gene and phenotype (affected or unaffected with BD-I) were found in non-perseverative errors (β=3.20 and Corrected P=0.0034) on the Wisconsin Card Sorting Test (WCST). The allele of this SNP denoted the positive effect on the WCST non-perseverative errors in BD-I patients group (β=2.80 and Corrected P=0.017). The genotypic association analyses also supported the findings (F=4.24 and P=0.007), but this effect was not found in controls. LIMITATIONS: The sample size was relatively small and the SNP coverage was limited, making it very important to be cautious when drawing a conclusion. CONCLUSIONS:DRD4 gene may play an important role in psychotic symptomatology rather than in unique diagnosis, BD, for example. A genetic association exists between DRD1 gene and impaired cognition in BD.
Authors: Candace R Lewis; Adrienne Henderson-Smith; Reagan S Breitenstein; Hayley A Sowards; Ignazio S Piras; Matthew J Huentelman; Leah D Doane; Kathryn Lemery-Chalfant Journal: Epigenetics Date: 2019-03-16 Impact factor: 4.528