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.
Guangzhou Brain Hospital, Affilated Brain Hospital of Guangzhou Medical University, No. 36 Minxin Road, Liwan District, Guangzhou 510370, PR China.
J Affect Disord. 2015 Jan 1;170:85-90. doi: 10.1016/j.jad.2014.08.039. Epub 2014 Sep 2.
To determine the correlation among the polymorphisms of dopamine receptor genes, cognitive function of Bipolar disorder (BD) patients, and BD.
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.
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.
The sample size was relatively small and the SNP coverage was limited, making it very important to be cautious when drawing a conclusion.
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.
确定多巴胺受体基因多态性与双相障碍（BD）患者认知功能及 BD 之间的相关性。
采用 Illumina GoldenGate 基因分型检测技术，对 375 例双相 I 型障碍（BD-I）患者（患者组）和 475 名健康对照（对照组）中的 23 个多巴胺受体基因的单核苷酸多态性（SNP）进行基因分型。对 158 例临床稳定的患者和 307 例与患者年龄、性别和教育程度相匹配的健康对照进行认知功能测试。
DRD4 基因启动子区 rs3758653 等位基因频率在患者组和对照组之间差异有统计学意义（χ²=9.386，校正 P=0.046）。在有精神病症状的 BD-I 患者和健康对照组之间也观察到了这种显著差异（χ²=9.27，校正 P=0.049）。BD-I 患者在所有认知领域的表现均明显差于健康对照组（p<0.01），除 TMTA 错误和非法时间外。在威斯康星卡片分类测试（WCST）的非持续错误中，发现 DRD1 基因 rs5326 多态性与表型（是否患有 BD-I）之间存在显著交互作用（β=3.20，校正 P=0.0034）。该 SNP 的等位基因对 BD-I 患者组 WCST 非持续错误有正向影响（β=2.80，校正 P=0.017）。基因分型关联分析也支持这一发现（F=4.24，P=0.007），但在对照组中未发现这种效应。
样本量相对较小，SNP 覆盖率有限，因此在得出结论时要非常谨慎。
DRD4 基因可能在精神病症状中而非独特诊断（如 BD）中发挥重要作用。DRD1 基因与 BD 患者认知障碍之间存在遗传关联。
